Effect of cystic fibrosis on inhaled aerosol boluses

An aerosol bolus undergoes changes in shape between its inspiration and expiration. In comparison with the inhaled bolus, the exhaled bolus is more spread because of convective mixing, may have a shift in the location of the mode caused by asymmetries of filling and emptying of lung units, and contains fewer particles because of particle deposition. We hypothesized that the extent of these changes is related to lung health. To examine this, 11 patients with cystic fibrosis (CF) and 11 healthy subjects inhaled 70 cm3 boluses containing 1 micron monodisperse particles that were inspired to volumetric penetrations (Vp) of 100 to 700 cm3. As each bolus was expired, we measured spreading (volumetric width at one-half aerosol concentration peak height), modal shift, and particle deposition. Patients with CF exhaled boluses that were broader than those exhaled by normal subjects at all penetrations examined. At a Vp of 600 cm3, patients had a mean bolus half-width that was 68% greater than that of healthy subjects (p less than 0.0001), and they exhaled the bolus mode 20% earlier (p less than 0.0002). Particle deposition was increased compared with that in normal subjects at all Vp. For example, mean deposition at a Vp of 600 cm3 was 46.2 +/- 2.6% (SE) for the patients versus 25.8 +/- 1.6% for the normal subjects (p less than 0.0001). Among the patients with CF, pulmonary function parameters indicating obstruction were significantly correlated with bolus spreading and aerosol deposition: the percent predicted FEV1/FVC was inversely correlated with spreading (r = -0.88, p less than 0.0004) and deposition (r = -0.84, p less than 0.0008).(ABSTRACT TRUNCATED AT 250 WORDS)     

Adaptation in human subjects to the effects of inhaled ozone after repeated exposure.

Single exposures to low concentrations of ozone (0.4 to 0.5 ppm) have resulted in decrements in forced vital capacity and specific airway conductance. To establish whether adaptation might occur with repeated exposure, 14 normal human subjects were exposed on 5 consecutive days to 0.4 ppm of ozone for 3 hours per day in an environmental chamber. Measurements of forced vital capacity and specific airway conductance obtained after exposure to ozone were compared to corresponding control values obtained during the previous week, when the same subjects breathed filtered air in the environmental chamber for 3 hours per day on 5 consecutive days at the same time of day. The forced vital capacity was significantly lower than the control value on the first 3 days of exposure to ozone, but there was no significant difference on the fourth and fifth days. Specific airway conductance was significantly lower than the control value on the first and second days of exposure to ozone; no significant difference was noted on the third, fourth, or final day. All subjects were symptomatic on the first and second days of exposure to ozone. Symptoms resolved thereafter, with only one subject remaining symptomatic on the final day of exposure to ozone.     

Cold effect on qt dispersion in healthy subjects

Thirty-one healthy subjects, aged 35 +/- 6 (21 to 48) years, were included in the study to evaluate the effect of ice water immersion on QT dispersion. There was no difference in the age between females (n = 11) and males (n = 20). Baseline, stress (at the end of ice water immersion, 4 degrees C, for 3 minutes) and recovery 12-lead electrocardiograms (ECGs) were recorded on each subject. During the test, a significant variability developed in both the QT dispersion (52 +/- 17, 68 +/- 25 and 59 +/- 21 ms; p = 0.015) and the corrected QT dispersion (56 +/- 17, 76 +/- 27 and 64 +/- 23 ms; p = 0.005), but not in the heart rate (74 +/- 11, 76 +/- 9, and 74 +/- 9 bpm, respectively; p = 0.447). There was no inter-sex difference in the baseline heart rate or QT dispersion, or in their response to ice water immersion. Age significantly correlated with the variation of QT dispersion to ice water immersion (r = 0.380, p = 0.035). With 37 years of age as a separation point, the variation of QT dispersion to ice water immersion was more obvious in the older group (28 +/- 22 vs. 10 +/- 19 ms, p = 0.023). In conclusion, cold may increase QT dispersion in healthy subjects, with a more obvious effect in the older ones.     

Effect of ozone exposure on airway responses to inhaled allergen in asthmatic subjects

BACKGROUND: Controlled human exposure studies have produced conflicting results regarding the effect of ozone on the early bronchoconstrictor response to inhaled allergen in specifically sensitized asthmatic subjects. Spirometric parameters do not necessarily reflect the airway inflammatory effects of inhaled ozone or allergen. OBJECTIVE: This study was designed to investigate whether exposure to ozone enhances the late airway inflammatory response, as well as the early bronchoconstrictor response, to inhaled house dust mite allergen in sensitized asthmatic subjects. DESIGN: Randomized, counter-balanced, cross-over study. SETTING: Human exposure laboratory. METHODS: Fourteen subjects were exposed to 0.2 ppm O(3) or filtered air, on separate days, for 1 h during exercise. After each exposure, the subjects were challenged with doubling doses of Dermatophagoides farinae (DF) allergen (provocative concentration of DF causing a 15% decrease in FEV(1) [PC(15)]). At 6 h after allergen challenge, bronchoscopy with BAL, proximal airway lavage (PAL), and endobronchial biopsy were performed. The second exposure/allergen challenge/bronchoscopy sequence was performed at least 4 weeks after the first sequence. RESULTS: No significant difference in cellular or biochemical markers of the late inflammatory response after allergen was found between the ozone and air exposures (although a trend toward increased neutrophils was noted after ozone exposure in the PAL fluid, p = 0.06). For the group as a whole, no significant difference in PC(15) was demonstrated after ozone exposure compared to air exposure. However, subjects with the greatest ozone-induced decrements in FEV(1) tended to have lower PC(15) values after ozone exposure. CONCLUSION: Exposure to a relatively low-level concentration of ozone does not enhance the late inflammatory or early bronchoconstrictor response to inhaled antigen in most allergic asthmatic subjects. Our results do suggest, however, that a subgroup of asthmatics may acquire increased sensitivity to aeroallergens after exposure to ozone.     

The effect of exercise on the deposition of an inhaled aerosol

We investigated the regional deposition in the lungs, of an inhaled submicron aerosol at rest and during exercise in 13 normal volunteers of whom 5 were cigarette smokers. The degree of exercise (VO2 approximately 2 L/min) was chosen to simulate moderately heavy physical labour. Tracheobronchial and alveolar components of deposition were measured by comparing images immediately after inhalation of aerosol and 24 h later when mucociliary clearance was complete. At rest almost all deposition was alveolar (97%). The increase in total deposition on exercise was of similar order to the increase in ventilation. On exercise regional alveolar deposition became more even, although basal still exceeded apical deposition. Tracheobronchial deposition on exercise was increased in all zones but particularly in the upper zones, thereby contrasting with the base to apex gradient of parenchymal deposition. These changes were exaggerated in the smokers. The increased upper zone tracheobronchial deposition may have implications in regard to the pathogenesis of diseases caused by the inhalation of dusts and fumes.     

Seasonal variability of the QT dispersion in healthy subjects

We studied the seasonal variability of QT dispersion in 25 healthy subjects, aged 36 +/- 5 (25 to 46) years. Four seasonal 12-lead rest electrocardiograms (ECGs) recorded at a double amplitude were performed at 25 mm/s at intervals of roughly 3 months. To avoid possible confusion from the circadian rhythm of QT dispersion, subsequent ECGs were recorded within 30 minutes of the reference summer one. The QT dispersion was calculated as the difference between the longest and the shortest mean QT intervals. There was a seasonal variability in the QT dispersion (P =.001), with the largest QT dispersion occurring in winter (66 +/- 21 ms) and the smallest one in spring (48 +/- 18 ms). In conclusion, there exists a seasonal variability of QT dispersion in healthy subjects and such variability should be taken into consideration in comparison of the QT dispersion.     

Effect of inhaled N-acetylcysteine on hydrogen peroxide exhalation in healthy subjects

N-acetylcysteine (NAC) has antioxidant properties and its oral administration decreased H(2)O(2) exhalation in patients with chronic obstructive pulmonary disease. In this study we tested whether inhaled NAC could suppress H(2)O(2) levels in exhaled breath condensate (EBC) of eight healthy subjects that have never smoked (never-smokers). Original NAC solution (ACC vial, 300 mg NAC in 3 ml solvent), NAC-placebo (vehicle), sterile 0.9% NaCl or distilled water were nebulized via the pneumatic De Vilbiss nebulizer once daily every 7 days and H(2)O(2) and thiols exhalation was measured just before, 30 min and 3 h after the end of drug administration. Additional in vitro experiments were performed to evaluate NAC stability during nebulization, reactivity with H(2)O(2) and possible H(2)O(2) generation in aqueous NAC solutions. NAC almost completely abolished H(2)O(2) exhalation 30 min after inhalation (0.02+/-0.04 vs. 0.21+/-0.09 microM, p<0.001). However, 3 h later the H(2)O(2) levels raised 1.8-fold from baseline (p<0.01). Other inhaled solutions did not affect H(2)O(2) levels. Mean thiol concentration in EBC rose (p<0.05) after treatment with NAC and reached 1.03+/-0.48 microM at 3 h. Although, 25 and 50 mM NAC completely inhibited H(2)O(2)-peroxidase-luminol-dependent chemiluminescence, detectable amounts of H(2)O(2) were generated in NAC solutions. It was accompanied by moderate loss of -SH groups. Catalase and ascorbic acid prevented H(2)O(2) formation in NAC solutions. In conclusion inhaled NAC revealed biphasic effect on H(2)O(2) exhalation in healthy subjects, which depends on direct H(2)O(2) scavenging and H(2)O(2) generation related to drug oxidation. The net result of these processes may determine anti- or pro-oxidant action of inhaled NAC.     

Seasonal variation of P-wave dispersion in healthy subjects

We studied the seasonal variability of P dispersion in 523 healthy male patients, aged 22 +/- 4 years (range, 20-26). Four seasonal 12-lead resting electrocardiograms were recorded at 2 mV/cm standardization and at 50 mm/s paper speed at intervals of three months. Electrocardiograms were recorded between the hours 10 to 12 AM. The difference between the maximum P-wave duration and minimum P-wave duration was calculated and defined as "P dispersion." There was a significant seasonal variation in the maximum P-wave duration (P = .001) and P dispersion (P = .001), with the longest maximum P-wave duration (121 +/- 16 ms) and P dispersion (41 +/- 7 ms) observed in winter and the shortest maximum P-wave duration (106 +/- 15 ms) and P dispersion (24 +/- 8 ms) observed in summer. The minimum P-wave duration did not show any significant seasonal variation. In conclusion, there exists a significant seasonal variation in the maximum P-wave duration and P dispersion in healthy patients. Seasonal variation of P dispersion resulted from the significant variation of maximum P-wave duration.     

Effect of repeated boluses of intravenous omeprazole and primed infusions of ranitidine on 24-hour intragastric pH in healthy human subjects

The aim of this study was to identify dosage regimens using intravenous omeprazole and ranitidine that would elevate and consistently maintain intragastric pH>6 in the first 24 hr of therapy. In 19 healthy, fasting human subjects using continuous 24-hr gastric pH-metry, we studied two dosages of primed infusions of ranitidine (50 mg bolus followed by infusion of either 3 or 6 mg/kg body wt/24 hr) and six regimens of intravenous omeprazole (80–200 mg in 24 hr in two to five boluses). Only the two ranitidine infusions and high doses of omeprazole (≥160 mg/day as four or five boluses) raised the intragastric median pH above 5.4. There was no significant difference in the median intragastric pH after high dose ranitidine and high doses of omeprazole. Considerable interindividual variation in intragastric pH was observed after omeprazole therapy. The percentage of intragastric pH>6.0 during the 24-hr study was lower after omeprazole (35–42%) than after high-dose ranitidine (58%). We conclude that it is possible to raise intragastric pH>6.0 by use of either primed ranitidine infusion or by repeated boluses of omeprazole. However, maintenance of this high pH in the first 24 hr is difficult with both, more so with omeprazole.     

Computerised measurements of QT dispersion in healthy subjects

Objective—To assess the stability and reproducibility of computerised QT dispersion (QTd) measurement in healthy subjects, as this is presently being incorporated into commercial electrocardiographic systems.
Methods—70 healthy volunteers (mean (SD) age 38 (10) years, 35 men, 35 women) with a normal 12 lead electrocardiogram (ECG) were studied. From each subject, 70 ECG recordings were taken using the MAC VU ECG recorder (Marquette). In study A, 50 ECGs were recorded in each subject: 10 supine, 10 sitting, 10 standing, 10 holding breath in maximum inspiration, and 10 holding breath in maximum expiration. After a mean interval of 8 (3) days (range 7 to 23), 10 recordings in supine and 10 in the standing position were repeated in each subject (study B). On measurements made using a research version of the commercial software without manual modification, the reproducibility of QTd was assessed by coefficient of variance (CV) and relative error, and comparisons made with other ECG indices.
Results—(1) QTd measurements were stable and not influenced by changes in posture and respiratory cycle; (2) there was no difference in QTd measurements between men and women, or between age groups dichotomised at 35 years; (3) no correlation was found between QTd and heart rate or QT interval; (4) short term reproducibility of all QTd measurements (CV 15.6% to 43.8%) was worse than that of conventional ECG indices (CV 1.4% to 5.3%); (5) long term reproducibility of QTd measurements (relative error 27.4% to 31.0%) was also worse than that of conventional ECG indices (relative error 1.8% to 7.9%) (p < 0.0001); (6) the reproducibility of QTd measurements tended to increase when several serial recordings were averaged.
Conclusions—Computerised measurements of global QTd and global QT-SD from 12 lead ECG by the MAC VU/QT Guard system are not significantly altered by changes in posture and respiration. The reproducibility of all QTd measurements is inferior to that of conventional ECG indices in healthy subjects.

Keywords: QT dispersion;  reproducibility;  automatic measurement;  healthy subjects     

小剂量奥美拉唑镁肠溶片对健康成人24小时胃内pH的影响

目的　奥美拉唑具有强大的抑制胃酸分泌的作用 ,常用剂量为 2 0mg。因此 ,探讨小剂量奥美拉唑镁肠溶片 (洛赛克MUPS ,1 0mg)对健康成人 2 4h胃内 pH变化的影响。 方法　利用Digitrap perMKⅢ动态 pH监测仪观察 1 2例健康志愿者 2 4h胃内pH变化节律 ,次日晨 8时口服奥美拉唑镁肠溶片 1 0mg ,并复查 2 4h胃内 pH。经过 1周清洗期后 ,其中 1 1例受试者再予以奥美拉唑镁肠溶片 1 0mg ,每日 1次 ,连续 6d ,并于第 6天复查 2 4h胃内pH。 结果　奥美拉唑镁肠溶片 1 0mg顿服后 ,2 4h胃内 pH中位值由 1 .0 0升高至 1 .2 0 ,2 4h胃内平均pH值、pH >3总时间百分比、pH >4总时间百分比及pH >5总时间百分比分别由 1 .56± 0 .34 ,(1 8.44± 7.55) % ,(1 2 .0 5± 6 .1 0 ) % ,(6 .89± 4 .40 ) %升高至 2 .1 8± 0 .65(P <0 .0 1 ) ,(34 .40± 1 2 .73) % (P <0 .0 1 ) ,(2 3 .58± 1 0 .59) % (P <0 .0 1 )及 (1 3 .58± 8.36) % (P <0 .0 5)。奥美拉唑镁肠溶片 1 0mg ,每日 1次 ,连续 6d后 ,2 4h胃内 pH中位值升高至 3 .2 0 ,2 4h胃内平均 pH值、pH >3总时间百分比、pH >4总时间百分比及 pH >5总时间百分比分别升高至 4 .30± 1 .61 ,(59.2 1± 2 1 .37) % ,(48.1 3± 2 3 .2 4 ) %及 (36 .85± 2 2 .62 ) % ,均显     

Acute ozone exposure increases plasma prostaglandin F2 alpha in ozone-sensitive human subjects

Twenty O3-sensitive and 2O O3-nonsensitive subjects participated in a study to investigate the effects of disparate O3 sensitivity on plasma prostaglandin F2 alpha) responses consequent to exposure to ambient O3 concentrations. Subjects were selected from a pool of 75 normal healthy college-aged males who had been previously exposed to 0.35 ppm O3 for 1 h at an exercising VE of 60 L/min. The selection criterion used was the observed decrement in FEV1 after the O3 exposure: O3-sensitive, FEV1 decrement greater than 24%; O3-nonsensitive, FEV1 decrement less than 11%. Each subject was exposed to filtered air and to 0.20 and 0.35 ppm O3 for 80 min while exercising at a VE of 50 L/min. These experimental protocols were divided into two 40-min sessions separated by a period of 4 to 10 min. PGF2 alpha, FVC, FEV1, and FEF25-75 were evaluated before, during, and after each protocol. SGaw and Vtg were measured before and after each protocol. Plasma PGF2 alpha was significantly increased in the O3-sensitive group during and after the 0.35-ppm O3 exposure.     

The effect of Ramadan fasting on spirometry in healthy subjects

OBJECTIVES: Lung function tests are an important investigative tool in diagnosing respiratory diseases, judging their severity and assessing prognosis. The primary aim of the present study was to assess whether Ramadan fasting affected normal lung function values. METHODOLOGY: Forty-six non-smoking healthy males, with a mean age of 24.2 years (SD 6.4 years) were investigated. Spirometry was performed according to the recommendations of the American Thoracic Society. Days between the 15th and 25th of three Islamic months (pre-Ramadan, Ramadan and post-Ramadan) were selected for spirometry. On all three occasions, FVC, FEV(1), FEV(1)/FVC%, maximum voluntary ventilation (MVV(indirect)), PEF, FEF(25--75%) and body mass were measured. Pre- and post-Ramadan readings were compared with the readings during Ramadan fasting. The results were analysed by repeated measures analysis of variance. RESULTS: No significant change was seen in lung function during Ramadan as compared to the pre-Ramadan period. FVC was decreased significantly in the post-Ramadan period compared to Ramadan and this period was associated with a significant increase in body mass. CONCLUSION: Relative to pre-Ramadan baseline values, there was no change in spirometry during Ramadan fasting in these subjects.     

The effect of rivastigmine on sleep in elderly healthy subjects

Previous research has shown that acetylcholinesterase inhibitors may affect REM sleep, however, results are inconclusive. From the present findings it is concluded that the effects of rivastigmine, a reversible acetycholinesterase inhibitor, on REM sleep are more pronounced in the elderly where we found REM latency to be significantly reduced. This may be explained by better bioavailability and/or by reduced stability of the circadian rhythmicity in elderly individuals. Because rivastigmine is used in the treatment of Alzheimer's disease, further research investigating the relationship between the REM enhancing properties of rivastigmine and cognitive functioning seems promising.     

The effect of hyperinflation on lung elasticity in healthy subjects

In acute severe asthma, lung distensibility may increase. To determine whether hyperinflation alon can increase lung distensibility acutely total lung capacity (TLC) and static volume-pressure (VP) properties were mesured in six healthy subjects after quiet breathing, and two periods of hyperinflation of 20–60 min, with negative pressure assistance at the chest wall (NPA) in one period and positive airways pressure assistance (PPA) in the other. In five subjects there was no change with NPA; with PPA lung volume at a static transpulmonary pressure of 10 cm H₂O (VL 10) increased by 0.3 L (P < 0.01) and K, the shape constant of an exponential function fitted to the deflation VP curve, increased (P < 0.001) without a change in TLC. In Subject 6, with both NPA and PPA, VL 10 increased (P < 0.001 with NPA; P < 0.01 with PPA); volume hysteresis was unchanged. The small increased of lung distensibility in five subjects after PPA we attribute to decreased pulmonary blood volume; in Subject 6 the changes with hyperinflation suggest decreased tissue forces. We conclude that hyperinflation can cause an acute increase in lung distensibility in some individuals. The variable response between subjects parallels that seen in astma.     

Fluctuation and reproducibility of exposure and effect of insulin glargine in healthy subjects

Aim: Low diurnal fluctuation and high day‐to‐day reproducibility in exposure and effect characterize beneficial basal insulin products. Two insulin glargine (LANTUS) formulations [without (R) or with polysorbate‐20 (T)], added to minimize unfolding of proteins and subsequent formation of fibril structures, were assessed for equivalence in exposure and effect, and aspects of fluctuation and reproducibility in time–concentration and time–action profiles. Methods: A dose of 0.4 U/kg was subcutaneously administered to 24 healthy subjects in a two‐sequence (R‐T‐R‐T or T‐R‐T‐R), randomized, four‐way crossover trial utilizing 30‐h Biostator‐based euglycaemic glucose clamps. Results: Identical serum insulin glargine concentration and time–action profiles established average, individual and population equivalence in insulin exposure and effect. Point estimates for 24‐h area under the curve for insulin (INS–AUC_{0–24 h}) and glucose infusion rates (GIR–AUC_{0–24 h}) were 97% [90% confidence interval (CI): 91–103%] and 100% (88–114%), respectively. Within‐subject variability (coefficient of variation) for INS–AUC_{0–24 h} and GIR–AUC_{0–24 h} were 19% (95% CI: 14–25%) and 34% (24–43%), respectively. The diurnal relative fluctuation of the serum insulin glargine concentration was 20% (95% CI: 19–21%). Conclusion: Insulin glargine in either formulation presents with a high day‐to‐day reproducibility of a uniform release after injection enabling an effective basal insulin supplementation.     

Effect of ozone on bronchial mucosal inflammation in asthmatic and healthy subjects

Epidemiological studies suggestthat asthmatics are more affected by ozone than healthy people. This study tested three hypotheses (1) that short-term exposure to ozone induces inflammatory cell increases and up-regulation of vascular adhesion molecules in airway lavages and bronchial tissue 6 h after ozone exposure in healthy subjects; (2) these responses are exaggerated in subjects with mild allergic asthma; (3) ozone exacerbates pre-existent allergic airways inflammation. We exposed 15 mild asthmatic and 15 healthy subjects to 0.2 ppm of ozone or filtered air for 2 h on two separate occasions. Airway lavages and bronchial biopsies were obtained 6 h post-challenge. We found that ozone induced similar increases in bronchial wash neutrophils in both groups, although the neutrophil increase in the asthmatic group was on top of an elevated baseline. In healthy subjects, ozone exposure increased the expression of the vascular endothelial adhesion molecules P-selectin and ICAM- 1, as well as increasing tissue neutrophil and mast cell numbers. The asthmatics showed allergic airways inflammation at baseline but ozone did not aggravate this at the investigated time point. At 6 h post-ozone-exposure, we found no evidence that mild asthmatics were more responsive than healthy to ozone in terms of exaggerated neutrophil recruitment or exacerbation of pre-existing allergic inflammation. Further work is needed to assess the possibility of a difference in time kinetics between healthy and asthmatic subjects in their response to ozone.