BACKGROUND:Impaired exercise tolerance is frequently observed in patients with COPD. Respiratory muscle endurance training (RMET) by means of normocapnic hyperpnea can be used to improve respiratory muscle function and probably exercise capacity. RMET is not applied on a large scale because complicated equipment is needed to maintain carbon dioxide homeostasis during hyperpnea, which can also be done by enlarging the dead space of the ventilatory system by breathing through a tube. Therefore, tube breathing might be a new, inexpensive method for home-based RMET. The aim of this study was to assess whether home-based RMET by means of tube breathing improves endurance exercise performance in patients with COPD.METHODS:We randomized 36 patients with moderate-to-severe COPD to RMET by paced tube breathing (n = 18) or sham training (control, n = 18). Both groups trained twice daily for 15 min, 7 days per week, for 5 weeks.RESULTS:Patients receiving RMET showed significant improvements in endurance exercise capacity (constant-load exercise on cycle ergometry; 18 min vs 28 min, p < 0.001), in perception of dyspnea (Borg score; 8.4 vs 5.4, p < 0.001), and respiratory muscle endurance capacity (sustainable inspiratory pressure; 25 cm H(2)O vs 31 cm H(2)O, p = 0.005). Quality of life (chronic respiratory disease questionnaire) also improved (78.7 to 86.6, p = 0.001). The control group showed no significant changes.CONCLUSION:Home-based RMET by means of tube breathing leads to a significant improvement of endurance exercise capacity, a reduction in perception of dyspnea, and an improvement in quality of life in patients with moderate-to-severe COPD.

Dose delivery (total emitted dose, or TED) from dry powder inhalers (DPIs), pulmonary deposition, and the biological effects depend on drug formulation and device and patient characteristics. The aim of this study was to measure, in vitro, the relationship between parameters of inhalation profiles recorded from patients, the TED and fine particle mass (FPM) of Diskus and Turbuhaler inhalers. Inhalation profiles (IPs) of 25 patients, a representative sample of a wide range of 1500 IPs generated by 10 stable asthmatics, 3 x 16 (mild/moderate/severe) COPD patients and 15 hospitalized patients with an exacerbation asthma or COPD, were selected for each device. These 25 IPs were input IPs for the Electronic Lung (a computerdriven inhalation simulator) to determine particle size distribution from Ventolin Diskus and Inspyril Turbuhaler. The TED and FPM of Diskus and FPM of Turbuhaler were affected by the peak inspiratory flow (PIF) and not by slope of the pressure-time curve, inhaled volume and inhalation time. This flow-dependency was more marked at lower flows (PIF < 40 L/min). Both the TED and FPM of Diskus were significantly higher as compared to those of the Turbuhaler [mean (SD) TED(_diskus) (%label claim) 83.5 (13.9) vs. TED(_turbuhaler) (72.5 (11.1) (p = 0.004), FPM(_diskus) (%label claim) 36.8 (9.8) vs FPM(_turbuhaler) (28.7 (7.7) (p < 0.05)]. The TED and FPM of Diskus and FPM of Turbuhaler were affected by PIF, the flow-dependency being greater at PIF values below 40 L/min. Lower PIFs occurred more often when using Turbuhaler than Diskus, since Turbuhaler have a higher resistivity, requires substantially higher pressure in order to generate the same flow as Diskus. TED, dose consistency and the FPM were higher for Diskus as compared to Turbuhaler. The flow dependency of TED and FPM was substantially influenced by inhalation profiles when not only profiles of the usual outpatient population were included but also the real outliers from exacerbated patients.

The aim of this exploratory study was to investigate associations between sick leave in workers with asthma or COPD and disease-related variables, psychosocial variables, and work characteristics. Hundred and eighty-nine patients with physician-diagnosed asthma (N=118) or COPD (n=71) who had paid work in the past 12 months completed questionnaires on sick leave, health complaints, functional limitations, work characteristics and psychosocial issues, and underwent a pulmonary function test (FEV1 and FVC before and after bronchodilation). Logistic regression analyses were performed to investigate variables independently associated with high sick leave (i.e. more than twice a year and/or longer than 1 month per episode). Asthma patients, not having an emotionally difficult job, with low job satisfaction, who had changed employers, utilized job control, and who encountered pulmonary aggravating factors at work were found to have a higher incidence of sick leave. COPD patients, who had informed the employer or colleagues about the disease, who did not have difficult tasks at work, who did not hide dyspnea and limitations, and who reported high fatigue were showing higher sick leave. FEV1 and FVC were not associated with sick leave in either group. It was concluded that psychosocial variables, work characteristics, functional limitations, and complaints play a more important role in sick leave in workers with asthma and COPD than FEV1.

Objective: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire.Methods: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched, rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers.Results: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b=0.262mm/year; P=0.72). There was no agreement between the questionnaire and tremor severity (r=0.093; P=0.53). Postural tremor showed no significant difference between the first and third session (P=0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72).Discussion: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.

Background: Acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are associated with increased airflow limitation, hyperinflation and respiratory muscle fatigue. It is unclear, whether patients are able to perform adequate inhalations through various inhalation devices with different orfices during an exacerbation.The aim of this study was to examine the evolution of inhalation profiles of patients inhaling through Diskus, Turbuhaler, pressurized metered dose inhaler (pMDI) and Volumatic and consequently the appropriateness of using the various devices during an exacerbation.Measurements: 15 hospitalized patients participated in this randomized comparison of inhalation profiles through the four placebo-devices. For each device, triplicate inhalation profiles were recorded during day 1-9 of admission and in stable phase (day 50).Results: The mean percentage of patients performing optimum inhalation profiles was 100% for Diskus, 60% for Turbuhaler, 14% for pMDI and 87% for Volumatic over the interval of day 1-9 and day 50. Patients with an inspiratory muscle strength (MIP) of less than 6kPa were generally unable to generate the optimum flow through the Turbuhaler (>60 l/min).Conclusion: The Diskus and Volumatic can be used effectively in the acute phase of an exacerbation of asthma or COPD. The Turbuhaler could be optimally used after the fifth day of convalescence. The pMDI is rather unsuitable during an exacerbation. (C) 2004 Elsevier Ltd. All rights reserved.

Objective: The In Check Dial was developed to evaluate whether a patient is able to generate an adequate peak inspiratory flow (PIF) through a certain inhalation device. The inhalation profile recorder (IPR) is a calibrated instrument that measures flows through Diskus and Turbuhaler in our research setting. The aim of this study was to compare the PIFs of patients when inhaling through a Diskus or Turbuhaler connected with the IPR (PIF_diskus and PIF_TH) to the flows through the corresponding orifices of the In Check Dial (Diskus_In Check and TH_In Check). Methods: Twenty-four stable asthma and twenty-one chronic obstructive pulmonary disease (COPD) patients inhaled, on two separate occasions, in randomised order, via the Diskus or Turbuhaler connected with the IPR. Subsequently, patients inhaled through the In Check Dial using the orifices of Diskus or Turbuhaler. Results: The difference between Diskus_In Check and PIF_diskus was 3.9 (11.9) l/min (P=0.038). The difference between TH_In Check and PIF_TH was 3.5 (10.6) l/min (NS). All Diskus- and Turbuhaler-inhalations were performed with the minimum required flow of 30 l/min. However, four COPD patients inhaled with the non-optimal flow (<60 l/min) through the Turbuhaler. The In Check Dial did not indicate two of them. Conclusion: Measuring PIF through Diskus and Turbuhaler using the IPR and the In Check Dial, respectively shows a disagreement of 3.9 l/min. A disagreement of 3.5 l/min was found for the Turbuhaler. The In Check Dial did not identify two of four patients as ‘non-optimal’ users.

The oxygen cost of eccentric exercise is lower than that of concentric exercise at similar work-loads. In this study, the response to eccentric cycle exercise training (EET) in addition to general exercise training (GET) on exercise performance and quality of life was investigated in 24 patients with severe chronic obstructive pulmonary disease (COPD). All patients had a normal resting PaO2 and an arterial oxygen saturation (SaO2) below 90% at Wmax, achieved during a maximal incremental concentric cycle exercise test. The patients participated in a comprehensive inpatient pulmonary rehabilitation programme of 10 weeks. They were randomly assigned either to GET (GET group: mean FEV1 38% predicted) or to GET and additional EET (GET/EET group: FEV1 45% predicted). During EET, the patients were able to cycle eccentrically for 15 min continuously at a mean of 160 (69%) of Wmax whereas the Borg dyspnoea score did not exceed 3.0 and SaO2 did not fall below 90%. Parameters of cardiocirculatory fitness and gas exchange improved in the GET/EET group but no further improvement in exercise capacity occurred compared to GET. It is concluded that eccentric cycle exercise is a safe and attractive training modality for patients with severe COPD and can be performed at a high intensity without the patient becoming out of breath or needing supplemental oxygen.

Turbuhaler and Salbutamol-Diskus produce therapeutic doses at peak inspiratory flow (PIF) of >30 L/min. However, the optimum flow for Fluticasone-Diskus and Turbuhaler, in terms of total emitted dose and fine particle mass, is >60 L/min. The Turbuhaler achieved a higher output at this flow, as compared to Diskus. For pMDI 25 < PIF < 90 L/min, an actuation time of 0.0-0.2 sec is optimal. The aim of this study was to examine the incidence of optimum inhalation profiles, the effect of instruction, reproducibility, and the relationship between inhalation profiles and patient characteristics in stable asthmatics and mild/moderate/severe COPD patients. For each device, triplicate inhalation profiles were recorded during 6 sessions in a 10-week period. All patients achieved PIF > 30 L/min using Diskus. After instruction, all Diskus inhalations were performed with >60 L/min, except 7% of the inhalations of the severe COPD patients. At least 95% of the Turbuhaler inhalations was also performed with the minimum flow; however, 19% of the inhalations of the severe COPD patients were not optimally performed. The hand-lung coordination was inadequate in 40% of pMDI inhalation profiles, and 80% was performed with a too high flow. The reproducibility of PIF of both dry powder inhalers (DPIs) was very high (coefficient of variation = 4-10%). The reproducibility of the pMDI variables was lower (coefficient of variation = 9-18%). The major lung function variables predictive for PIF(diskus) and PIF(turbuhaler) were maximal inspiratory mouth pressure (MIP), PIF, and inspiratory capacity. No significant predictive lung function variables for PIF(pMDI) were found. Most patients performed reproducible optimum inhalation profiles through Diskus and Turbuhaler. However, in the severe COPD group, 7-19% of the patients were not able to generate the optimum flows through the DPIs. For these patients, a flow-independent aerosol delivery system might be more suitable. The majority of patients were using the pMDI incorrectly. Instruction had no effect. So, we concluded that the pMDI should not be used in these patient groups because of the coordination problems.

Regular use of beta2-agonists might result in increased bronchial hyper-responsiveness (BHR) and decreased forced expiratory volume in 1 sec (FEV1). It has been suggested that these possible detrimental effects are not a real deterioration of the disease, but that it might be only a transient (rebound) effect shortly after discontinuing this regular use. Moreover, these effects are thought to occur especially during short-acting and not during long-acting beta2-agonists use. The aim of this study was to invest gate whether a rebound effect (a pharmacological deterioration effect diminishing after several hours) in FEV1 and PC20 (concentration of histamine causing a 20% fall in FEV1 with regard to baseline) occurred after cessation of regular use of beta2-agonists, and whether this occurred both after short-acting and long-acting beta2-agonists. Allergic asthmatic patients (n = 134) were randomly allocated to the use of a short-acting (salbutamol), a long-acting beta2-agonist (formoterol) or placebo for 12 weeks (double-blind, double-dummy). No other asthma medication was allowed, including inhaled corticosteroids. At the start and every 4 weeks later FEV and PC20 were measured, each time at least 12 h after the last doses of study medication, which is in the possible rebound period. To investigate whether a (transient) rebound effect occurred, parameters were additionally measured at least 72 h later after discontinuation of the study medication. After 12 weeks of short-acting beta2-agonist use, a drop was seen in FEV1 from 85.6 (+/- 2.21)% predicted to 78.8 (+/- 2.9)% predicted, measured 15 h (median) after the last doses of medication. This was significantly different compared to placebo. When measured 168 h (median) later FEV1 recovered to 85.5 (+/- 2.4)% predicted, comparable to baseline. PC20 decreased with -1.17 (+/- 0.44) doubling dose after 12 weeks of short-acting beta2-agonist use, measured 15 h after the last doses of medication, which was significantly different compared to placebo. However, 168 h later PC20 recovered slightly with +0.55 (+/- 0.34) doubling dose, but this value was still lower compared to placebo. In contrast, during long-acting beta2-agonist and placebo use no significant changes were seen. In conclusion, the use of short-acting beta2-agonists resulted in a transient (rebound) effect in FEV while the effects on PC20 may point to a real deterioration of the disease. Long-acting beta2-agonist and placebo use showed no changes. We conclude that a mono-therapy of short-acting and not of long-acting beta2-agonists might have deleterious effects in asthma.

Asthma patients evaluate the effect of medication treatment through the degree of their asthma symptoms, which might be affected by their ability to perceive these symptoms. It has been suggested that beta(2)-agonists may mask the effects of an increase in airway inflammation. This study compared the perception of histamine-induced bronchoconstriction during monotherapy with short- or long-acting beta(2)-agonists.Asthmatic patients (68 male and 60 female, mean age 35+/-11 yrs, forced expiratory volume in one second (FEV1) 86+/-15%. of the reference value, provocative concentration causing a 20%, fall in FEV1 (PC20) geometric mean 0.97 mg(.)mL(-1) (95% confidence interval (CI): 0.73-1.30)) were selected and randomly allocated to use either a short-acting (salbutamol, n=41) or long-acting beta(2)-agonist (formoterol, n=46) or placebo (n=41) for 12 weeks. Perception of dyspnoea provoked by histamine-induced bronchoconstriction was measured at the start and every 4 weeks thereafter. Subjects quantified their sensation of breathlessness during the challenge tests on a modified Borg scale at the start of the study and every 4 weeks thereafter. The sensitivity to changes in FEV1 was analysed by the linear regression slope (a) Borg versus % fall in FEV1. The absolute perceptual magnitude (PS20) was determined by the perception score at the 20% fall in FEV1.Although the geometric mean PC20 decreased significantly within the group using short-acting beta(2)-agonists (in the group with initial PC20 greater than or equal to2 mg(.)mL(-1) there was a drop from 5.26-1.94 mg(.)mL(-1); p=0.013), repeated measurement analysis showed no difference in the course of time of perception (both slope a and PS20) between the three medication groups.This study showed that chronic use of short- or long-acting beta(2)-agonists in asthmatics for a period of 12 weeks, did not significantly change the perception of histamine-induced bronchoconstriction compared with placebo. Further investigation is required to establish whether this suggests that these drugs do not mask a deterioration of asthma.

Medroxyprogesterone acetate (MPA) and acetazolamide (ACET) are two ventilatory stimulants which are used in hypoxic and hypercapnic patients with chronic obstructive pulmonary disease (COPD). In a double-blind randomised study, the effects of a 2-week treatment with MPA (30 mg b.i.d.) or ACET (250 mg b.i.d.), followed by a 2-week treatment with a combination of both drugs (MPA/ACET), on daytime and nocturnal ventilatory and blood gas parameters in 17 stable hypercapnic COPD patients were investigated. ACET, MPA and MPA/ACET treatment decreased mean daytime carbon dioxide tension in arterial blood by 0.4, 0.7 and 1.2 kPa, respectively. Minute ventilation was improved only with combined therapy, from 9.3 to 11.2 L x min(-1). With MPA/ACET therapy, the hypercapnic and hypoxic ventilatory responses significantly increased, from 3.7 to 5.8 L x min(-1) x kPa(-1) and from -0.13 to -0.40 L x min(-1) x %(-1), respectively. The mouth exclusion pressure response to hypoxia increased during combination therapy, from -0.01 to -0.03 kPa %(-1). Nocturnal end-tidal carbon dioxide tension decreased with MPA and MPA/ACET treatment, by 0.9 and 1.4 kPa, respectively. MPA/ACET significantly increased mean nocturnal arterial oxygen saturation values, from 85.5 to 90.2%. The authors conclude that short-term combined treatment with medroxyprogesterone acetate and acetazolamide has a more favourable effect on day and night-time blood gas values and chemical drive than single drug treatment.

STUDY OBJECTIVE:To evaluate whether the discontinuation of furosemide treatment resulted in a decrease in PaCO(2) and an increase in daytime and nocturnal oxygenation.BACKGROUND:Furosemide is widely prescribed in patients with COPD for the treatment of peripheral edema. It is known that furosemide causes a metabolic alkalosis. A diminished chemoreceptor stimulation may cause a decreased alveolar ventilation.DESIGN:Randomized, double-blind, placebo-controlled, crossover trial.SETTING:Department of Pulmonology, Rijnstate Hospital Arnhem, the Netherlands.PATIENTS:Twenty patients with stable COPD (10 men; median age, 70 years [range, 58 to 81 years]; FEV(1) 35% predicted [range, 19 to 70% predicted]). Subjects were included if they had received furosemide, 40 mg/d, for the treatment of peripheral edema for at least a month and if they had a mean nocturnal arterial oxygen saturation (SaO(2)) < 92%. Patients with cardiac left and/or right ventricular dysfunction, sleep apneas, and patients receiving other diuretics, angiotensin-converting enzyme inhibitors, potassium or chloride replacement therapy, or long-term oxygen treatment were excluded.INTERVENTION:Furosemide was discontinued for 1 week and replaced by placebo treatment in the first or the second week.MEASUREMENTS AND RESULTS:Ventilation, daytime arterial blood gas levels, and nocturnal SaO(2) were measured at baseline, after 1, and after 2 weeks. Sixteen subjects completed the study. Ventilation increased from 10.4 L/min (range, 6.7 to 15.4 L/min) at baseline to 11.6 L/min (range, 8.7 to 14.0 L/min) after discontinuation of furosemide (p < 0.05). PaCO(2) decreased from 45 mm Hg (range, 35 to 64 mm Hg) to 41 mm Hg (range, 32 to 61 mm Hg; p < 0.01). Daytime and nocturnal oxygenation did not improve.CONCLUSIONS:Although it does not improve oxygenation, the discontinuation of furosemide decreases PaCO(2) in patients with COPD.

Aerosol delivery depends on device design and inhalation technique. In vitro device evaluations have shown that the emitted dose and fine particle mass of dry powder inhalers (DPIs) increase at high peak inspiratory flow rates (PIFR). Since the PIFR is mostly achieved after the release of the powder, slope of the pressure profile is also described as an important determinant. The aim of the present study was to assess whether the PIFR while using Diskus it and Turbuhaler it inhalers could be used to predict the slope of the inhalation pressure profile. In a group of 10 stable asthma patients and three groups (mild, moderate and severe) of 16 chronic obstructive pulmonary disease (COPD) patients, lung function was measured, and for each device, 18 inhalation profiles were recorded with the inhalation profile recorder during six sessions over 10 weeks. The values for the pressure slope and PIFR of both Diskus and Turbuhaler, were significantly correlated. The r-values were 0.865 and 0.882, respectively (p<0.01). Percentage explained variance was 74.8% for Diskus and 77.8% for Turbuhaler. Significant correlations were found between peak inspiratory flow rates and slopes. It has been shown for two different dry powder inhalers that peak inspiratory flow rate and slope correlate well in a wide range of patient groups.

STUDY OBJECTIVES COPD patients run a risk of developing nocturnal oxygen desaturation. When evaluating patients with nocturnal hypoxemia, an unfamiliar hospital environment and the monitoring equipment may cause sleep disturbances. It was hypothesized that increased sleep disruption will lead to fewer instances of desaturation during a night of monitoring. DESIGN The following forms of monitoring were evaluated prospectively on 3 nights for each patient: oximetry at home; polysomnography (PSG) at home; and PSG in the hospital. SETTING Department of Pulmonology, Rijnstate Hospital Arnhem, The Netherlands. PATIENTS Fourteen stable COPD patients (7 men; median age, 71.5 years; age range, 59 to 81 years; FEV(1), 32.5% predicted; FEV(1) range, 19 to 70% predicted) participated in the study. All subjects had significant instances of nocturnal arterial oxygen desaturation. Those patients with a sleep-related breathing disorder or cardiac failure were excluded from the study. MEASUREMENTS AND RESULTS The mean nocturnal arterial oxygen saturation (SaO(2)) level was higher during PSG monitoring at home (89.7%; range, 77 to 93%) than during oximetry monitoring (88.5%; range, 80 to 92%) [p < 0.025]. The fraction of time spent in hypoxemia (ie, SaO(2) < 90%) was lower during PSG monitoring at home (40.8%; range, 5 to 100%) than during oximetry monitoring (59.9%; range, 6 to 100%) [p < 0.01]. Desaturation time (DeltaSaO(2) > 4%) was lower during PSG monitoring at home (22.1%; range, 3 to 63%) during PSG monitoring at home than during oximetry monitoring (50.4%; range, 4 to 91%) [p < 0.01]. A correction for actual sleep during PSG monitoring reduced the differences between PSG monitoring at home and oximetry monitoring, although a difference in the desaturation time remained (PSG monitoring at home, 31.9% [range, 2 to 75%]; oximetry monitoring, 50.4% [range, 4 to 91%]) [p = 0.041]. A comparison of sleep architectures for nights when PSG was being monitored showed a higher arousal index in the hospital than at home (PSG monitoring in the hospital, 5.6 arousals per hour [range, 2 to 16 arousals per hour]; PSG monitoring at home, 2.5 arousals per hour [range, 1 to 6 arousals per hour]) [p < 0.025], but no differences in SaO(2) levels were found between PSG monitoring at home and PSG monitoring in the hospital. CONCLUSION The artifacts due to sleep-monitoring equipment may cause an underestimation of the degree of nocturnal hypoxemia in COPD patients. The addition of an unfamiliar environment causes more sleep disruption, but this does not affect nocturnal SaO(2) levels further.

BACKGROUND Some recent studies suggest that regular beta(2)-agonist use may result in inadequate control of asthma. It has been hypothesized that this occurs particularly in allergic asthmatic patients exposed to relevant allergens. Moreover, it is still unclear whether this occurs during the use of both short-acting and long-acting beta(2)-agonists. METHODS Asthmatic patients (n = 145) allergic to house dust mite (HDM) were randomly allocated to monotherapy with a short-acting beta(2)-agonist (SA; n = 48), a long-acting beta(2)-agonist (LA; n = 50), or placebo (n = 47), double blind, double dummy. The study covered three periods: (1) a 4-week run-in period, in which no changes took place; followed by (2) cessation of treatment with asthma medication including inhaled corticosteroids, introduction of allergen avoidance measures (active/placebo treatment) to lower HDM exposure in the active group, and an 8-week washout period to adjust patients to these changes; followed by (3) a 12-week study medication period. At the start of the 12-week medication period, and every 4 weeks thereafter, spirometric measurements (FEV(1) and provocative concentration of histamine causing a 20% fall in FEV(1) [PC(20)]) were performed. Peak flow and asthma symptoms were recorded daily. Additionally, at the start and every 6 weeks thereafter, dust samples were collected from mattresses and living room and bedroom floors to assess HDM (der p 1) concentrations. Effects on FEV(1), PC(20), peak flow, and asthma symptoms were analyzed with repeated-measurement analysis and corrected for the exposure to HDM allergens. RESULTS There were no significant differences among the three medication groups after 12 weeks for FEV(1). However, a significant decrease in mean FEV(1) percent predicted (95% confidence interval [CI]) was observed within the SA group: - 6.6 (- 10.4 to - 2.8) (p = 0.0002). A decrease in geometric mean PC(20) (95% CI) of - 1.2 (- 1.96 to - 0.44) doubling concentration was observed within the SA group (p = 0.05). No significant changes in FEV(1) and PC(20) were observed > 12 weeks within the LA group or the placebo group. There were neither changes in peak flow and asthma symptom scores among the three medication groups nor within the groups. Moreover, none of the parameters showed interactive effects with allergen exposure. CONCLUSION There were no significant differences among the three medication groups for FEV(1) and PC(20). The within-treatment group comparison showed a significant small decline in FEV(1) for the SA group (but not for the LA group), which could indicate that monotherapy with SAs might have negative effects on FEV(1). This was not seen during regular use of LAS: No clear pathophysiologic mechanism can explain these findings at the moment. Relatively high or low exposure to allergens did not alter these findings.

The relationship between asthma medication and the perception of asthma symptoms is of interest for daily practice. Poor perception of asthma symptoms might influence patients' health care behavior and subsequently might lead to undertreatment and deterioration of their disease. This study investigated the influence of the chronic use of short-acting and long-acting beta(2)-agonists, compared with the additional use of inhaled corticosteroids on the perception of histamine-induced bronchoconstriction. Patients with asthma (33 male and 31 female, mean age 35 +/- 11 yr, FEV(1) 87 +/- 14% of the reference value, PC(20) geometric mean 1.08 mg/ml (95% CI: 0.76-1.52) were selected and randomly allocated to the use of either a short-acting beta(2)-agonists (salbutamol, n = 22) or a long-acting beta(2)-agonists (formoterol, n = 22) or placebo (n = 20), which has been used for 12 wk. This medication treatment was repeated exactly 1 yr later, with patients receiving the same medication plus an inhaled corticosteroid. Perception of histamine-induced bronchoconstriction was measured at the start of each treatment period and every 4 wk thereafter. Subjects quantified their sensation of respiratory discomfort during the challenge tests on a modified Borg scale. The perceptive "sensitivity" for changes in FEV(1) was analyzed by the linear regression slope (alpha) "Borg versus percentage fall in FEV(1)." The "absolute perceptual magnitude" was determined by the perception score at the 20% fall in FEV(1) (PS(20)). The additional use of inhaled corticosteroids during the second year resulted in an improved perception of histamine-induced bronchoconstriction (slope alpha) compared with the first year for only the long-acting beta(2)-agonists group (p value 0.036). This improvement was not observed for the "absolute perceptual magnitude" (PS(20)). The additional use of inhaled corticosteroids during chronic use of long-acting beta(2)-agonists improves the perceptive "sensitivity" for changes in FEV(1) during histamine-induced bronchoconstriction, which was not observed for short-acting bronchodilators. This result might indicate that the positive effects on perception of airway obstruction might be another reason (besides the beneficial effects on the clinical condition) for prescribing a combination of long-acting beta(2)-agonists and inhaled steroids.

Objective: Verbal instruction and demonstration of inhalation technique are essential to enhance the effectiveness of inhalation therapy. Placebo devices are commonly used to instruct patients. It is not obvious that patients, who inhale with an adequate flow through an empty placebo Diskus®, would also be able to do so with active inhalers containing a strip with powder. The presence of powder may result in a change in resistivity. We compared the resistivities of a placebo Diskus® being empty; a powder filled Diskus® inhaler and a Diskus® inhaler with an empty blister. Methods: A Diskus® inhaler was placed in a box, which enabled measurement of pressure drop and flow rates. Ten placebo and ten Ventolin® Diskus® inhalers were measured. Twelve pressure- and flow-profiles were recorded through each device. After each simulated inhalation through a powder filled blister, a second inhalation was performed through the empty blister. The resistivity was calculated by pressure-flow equation. Results: The resistivity of the empty placebo Diskus® inhaler was slightly but significantly higher than both blister filled inhalers, with or without powder (0.0215 vs. 0.0211 and 0.0211 (kPa)0.5 (l min−1)−1) (P<0.001). Conclusion: Patients who are capable of generating sufficient flow through a placebo Diskus® will surely be capable of generating equivalent flows through a Diskus® inhaler containing a strip with active drug substance.

Acute metabolic alkalosis (NaHCO3), acidosis (NH4Cl), and placebo (NaCl) were induced in 15 healthy volunteers (12 females, median age 34 (range 24–56) years) in a double blind, placebo controlled study to evaluate the presence of the effects on airway calibre. Acid–base shifts were determined by capillary blood gas sampling. Measurements were performed at the maximal acid–base shift, 90 min after intervention. Airway resistance (Raw) and specific airway conductance (sGaw), were evaluated, as primary variables, pre and post intervention. Secondary variables, including bronchial responsiveness to histamine, maximal respiratory mouth pressures and grip strength, were evaluated post intervention. In alkalosis, base excess (BE) increased from –0.3 (−3.0–1.9) to 3.0 (1.0–4.8) mmol/l and pH increased from 7.41 (7.37–7.43) to 7.44 (7.39–7.47) (both P<0.01), accompanied by an increase in PaCO2: 4.7 (4.0–5.7) to 5.0 (4.7–6.1) kPa (P<0.05). Raw increased from 0.156 (0.134–0.263) to 0.169 (0.132–0.271) kPa s/L (P<0.05), sGaw decreased, but this was not statistically significantly. In acidosis, BE decreased from −0.2 (−2.0–2.2) to –3.5 (−6.3–1.1) mmol/l and pH decreased from 7.41 (7.39–7.45) to 7.36 (7.31–7.40) (both P<0.01), accompanied by a non-significant decrease in PaCO2. Changes in Raw and sGaw were contrary to those in alkalosis, but did not reach statistical significance. Acute metabolic acid–base shifts mildly influence the airway calibre in healthy human subjects.

BACKGROUND Some asthmatic patients perceive the severity of their disease rather poorly. These patients may not receive optimal therapy because of underpresentation of their respiratory symptoms. It is therefore important to identify these patients. The present study evaluates a new threshold loading device for measuring the perception of respiratory sensation. This method for measuring the perception of respiratory sensation may be a viable alternative to the bronchial provocation test. The aim of the present study was to investigate whether the assessment of the perception of respiratory sensation based on a threshold loading test (inspiratory and expiratory) identifies the same subjects as poor perceivers as compared to assessment by histamine bronchial provocation test. METHOD In 36 subjects, the perception of respiratory sensation through a threshold loading device was compared to the perception of respiratory sensation during a histamine provocation test. Each test was performed with scoring of the magnitude of the respiratory sensation on a visual analog scale (VAS). The magnitude of the stimulus intensity was indicated by the percentage of decrease in FEV(1) during the histamine challenge test and by the percentage of the subject's maximum mouth pressure (percent maximal inspiratory pressure and percent maximal expiratory pressure) during the threshold loading test. The relationship between VAS values and the stimulus intensity was analyzed by determining the linear regression coefficient between the two parameters. RESULTS No relationship was found between the perception of the sensation induced by the histamine challenge and that during breathing through a threshold loading device for both inspiration (Rs = 0.15; p = 0.40) and expiration (Rs = 0.13; p = 0.47). We did find a significant relation between the perception of respiratory sensation during the inspiratory and expiratory threshold loading test (Rs = 0.67; p = 0. 0001). Furthermore, we defined a subgroup of patients of special interest: those with low symptoms of breathlessness and high bronchial responsiveness. Compared to the inspiratory and expiratory threshold loading test, the histamine challenge test identified more patients in the special interest group as poorest perceivers. CONCLUSION The measurement of perception by means of a threshold loading device and a histamine provocation test did not identify the same subjects as poor perceivers, probably because we did not measure the patient's perceptiveness for exactly the same stimuli. In the population with relatively more severe asthma and very low symptoms of breathlessness, the histamine-induced bronchoconstriction test identified more patients as poorest perceivers compared to the threshold loading test.

Water-displacement volumetry can be used for quantifying the volume of the leg. However, not much is known about its application in patients with peripheral oedema of cardiopulmonary origin. We measured the reproducibility of a water-displacement apparatus with a solid object and in ten non-oedematous clinical patients (group A). The day-to-day variability of the leg volume was assessed in the same group. The diurnal variability was assessed in ten patients with persisting peripheral oedema (group B). The effect of treatment on the severity of peripheral oedema was evaluated in another nine patients with peripheral oedema, who were in need of diuretic treatment (group C). Volumetric results were compared to the ankle circumference method and the body weight method. The coefficient of variation was 0.16% in the fixed object and 0.47% in group A. The day-to-day variability was 1.52% after 1 day and 1.76% after a mean interval of 4.8 days. In group B, leg volume and circumference increased during the day (5.9%, P<0.001, and 24%, P<0.01, respectively), while body weight remained unchanged. In group C, leg volume, circumference and body weight decreased significantly after treatment (13.1%, P<0.01, 71%, P<0.05, and 5.9%, P<0.05). The correlation between the changes in volume and body weight was poor (r = 0.37, P = 0.33). In conclusion, (1) water-displacement volumetry is highly reproducible, (2) a diurnal variability of peripheral oedema was found, and (3) volumetry is a suitable tool for monitoring peripheral oedema, while the body weight method appears to be less accurate.