'Exacerbation-free time' to assess the impact of exacerbations in patients with chronic obstructive pulmonary disease (COPD): a prospective observational study.

COPD exacerbations are commonly quantified as rate per year. However, the total amount of time a patient suffers from exacerbations may be stronger related to his or her disease burden than just counting exacerbation episodes. In this study, we examined the relationship between exacerbation frequency and exacerbation-free time, and their associations with baseline characteristics and health-related quality of life. A total of 166 COPD patients reported symptom changes during 12 months. Symptom-defined exacerbation episodes were correlated to the number of exacerbation-free weeks per year. Analysis of covariance was used to examine the effects of baseline characteristics on annual exacerbation frequency and exacerbation-free weeks, Spearman's rank correlations to examine associations between the two methods to express exacerbations and the Chronic Respiratory Questionnaire (CRQ). The correlation between exacerbation frequency and exacerbation-free weeks was -0.71 (p < 0.001). However, among frequent exacerbators (i.e., ≥3 exacerbations/year, n = 113) the correlation was weak (r = -0.25; p < 0.01). Smokers had less exacerbation-free weeks than non-smokers (ß = -5.709, p < 0.05). More exacerbation-free weeks were related to better CRQ Total (r = 0.22, p < 0.05), Mastery (r = 0.22, p < 0.05), and Fatigue (r = 0.23, p < 0.05) scores, whereas no significant associations were found between exacerbation frequency and CRQ scores. In COPD patients with frequent exacerbations, there is substantial variation in exacerbation-free time. Exacerbation-free time may better reflect the burden of exacerbations in patients with COPD than exacerbation frequency does.

Pre-operative functional mobility as an independent determinant of inpatient functional recovery after total knee arthroplasty during three periods that coincided with changes in clinical pathways.

AIMS: To investigate whether pre-operative functional mobility is a determinant of delayed inpatient recovery of activities (IRoA) after total knee arthroplasty (TKA) in three periods that coincided with changes in the clinical pathway. PATIENTS AND METHODS: All patients (n = 682, 73% women, mean age 70 years, standard deviation 9) scheduled for TKA between 2009 and 2015 were pre-operatively screened for functional mobility by the Timed-up-and-Go test (TUG) and De Morton mobility index (DEMMI). The cut-off point for delayed IRoA was set on the day that 70% of the patients were recovered, according to the Modified Iowa Levels of Assistance Scale (mILAS) (a 5-item activity scale). In a multivariable logistic regression analysis, we added either the TUG or the DEMMI to a reference model including established determinants. RESULTS: Both the TUG (Odds Ratio (OR) 1.10 per second, 95% confidence intervals (CI) 1.06 to 1.15) and the DEMMI (OR 0.96 per point on the 100-point scale, 95% CI 0.95 to 0.98) were statistically significant determinants of delayed IRoA in a model that also included age, BMI, ASA score and ISAR score. These associations did not depend on the time period during which the TKA took place, as assessed by tests for interaction. CONCLUSION: Functional mobility, as assessed pre-operatively by the TUG and DEMMI, is an independent and stable determinant of delayed inpatient recovery of activities after TKA. Future research, focusing on improvement of pre-operative functional mobility through tailored physiotherapy intervention, should indicate whether such intervention enhances post-operative recovery among high-risk patients. Cite this article: Bone Joint J 2017;99-B:211-17.

A cross-sectional study to assess the long-term health status of patients with lower respiratory tract infections, including Q fever.

Patients with a lower respiratory tract infection (LRTI) might be at risk for long-term impaired health status. We assessed whether LRTI patients without Q fever are equally at risk for developing long-term symptoms compared to LRTI patients with Q fever. The study was a cross-sectional cohort design. Long-term health status information of 50 Q fever-positive and 32 Q fever-negative LRTI patients was obtained. Health status was measured by the Nijmegen Clinical Screening Instrument. The most severely affected subdomains of the Q fever-positive group were 'general quality of life' (40%) and 'fatigue' (40%). The most severely affected subdomains of the Q fever-negative group were 'fatigue' (64%) and 'subjective pulmonary symptoms' (35%). Health status did not differ significantly between Q fever-positive LRTI patients and Q fever-negative LRTI patients for all subdomains, except for 'subjective pulmonary symptoms' (P = 0·048).

Optimizing referral of patients with neuromuscular disorders to allied health care.

BACKGROUND AND PURPOSE: To report the predictive validity of the perceived limitations in activities and need questionnaire (PLAN-Q), a screening instrument to support neurologists to select patients with neuromuscular disorders (NMD) for referral for a one-off consultation by occupational therapist (OT), physical therapist (PT) and speech therapist (ST). METHODS: In a cross-sectional validation study, 102 patients with various NMD participated. Patients received a one-off consultation by an expert OT, PT and ST and filled out the PLAN-Q. Therapists rated the appropriateness of the one-off consultations based on need, available treatment and patient's motivation. Receiver Operation Characteristic analysis and multivariate logistic regression analysis were used to obtain a PLAN-Q based prediction model for the appropriateness of the one-off consultations. RESULTS: Probability for a one-off OT consultation increased from 64% to 78% (95% CI: 69-85%). Prior test probability for a one-off ST consultation increased from 44% to 61% (95% CI: 48-73%). Prior test probability for one-off PT consultation could not be increased. CONCLUSION: Screening patients with NMD using the PLAN-Q may assist neurologists in selecting the appropriate patients for a one-off consultation by OT and ST. Unlike our expectations the screening did not guide referral for a one-off consultation by PT.

Influence of behaviour and risk factors on motor performance in preterm infants at age 2 to 3 years.

The aim of this cross-sectional study was to determine the influence of test-taking behaviour and risk factors for delayed motor performance in 437 preterm infants (244 males, 193 females; < or = 32 weeks of gestation) at the corrected age of 2 to 3 years (mean 29mo [SD 3.3]). Other mean (SD) sample demographics were: postmenstrual age 29(+5) weeks (1(+5)), range 25(+0)-32(+0); birthweight 1213.7g (331.7), range 468-2350; and days in the neonatal intensive care unit 21.1 (21.3), range 1-165. Children (n=23) with a severe disability were excluded. We assessed motor performance and behaviour during testing with the Motor Scale and the Behaviour Rating Scale (BRS) of the Bayley Scales of Infant Development, 2nd edition (BSID-II). Risk factors were tested against delayed motor performance as the dependent variable in binary logistic regression analysis. Median score on the Motor Scale in terms of the BSID-II Psychomotor Developmental Index (PDI) was 86. 'Delayed' motor performance was observed in 46.5% of the children tested, and behaviour was 'not-optimal' in 31.4%. The Motor Scale and BRS scores were significantly correlated (r(s)=0.62, p<0.01). Risk factors for delayed motor performance were: neonatal convulsions (odds ratio [OR] 4.5; 95% confidence interval [CI] 1.6-12.9), low maternal educational level (OR 3.3; 95% CI 1.7-6.5), male sex (OR 2.8; 95% CI 1.8-4.3), and chronic lung disease (OR 2.1; 95% CI 1.1- 4.1). We conclude that preterm infants are at high risk of delayed motor performance and non-optimal test-taking behaviour.

Impact of a spirometry expert system on general practitioners' decision making.

The present study assessed the impact of computerised spirometry interpretation expert support on the diagnostic achievements of general practitioners (GPs), and on GPs' decision making in diagnosing chronic respiratory disease. A cluster-randomised controlled trial was performed in 78 GPs who each completed 10 standardised paper case descriptions. Intervention consisted of support for GPs' spirometry interpretation either by an expert system (expert support group) or by sham information (control group). Agreement of GPs' diagnoses was compared with an expert panel judgement, which served as the primary outcome. Secondary outcomes were: additional diagnostic test rates; width of differential diagnosis; certainty of diagnosis; estimated severity of disease; referral rate; and medication or nonmedication changes. Effects were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). There were no differences between the expert support and control groups in the agreement between GPs and expert panel diagnosis of chronic obstructive pulmonary disease (OR (95% CI) 1.08 (0.70-1.66)), asthma (1.13 (0.70-1.80)), and absence of respiratory disease (1.32 (0.61-2.86)). A higher rate of additional diagnostic tests was observed in the expert support group (2.5 (1.17-5.35)). Computerised spirometry expert support had no detectable benefit on general practitioners' diagnostic achievements and the decision-making process when diagnosing chronic respiratory disease.

Limited evidence for effects of diet for type 2 diabetes from systematic reviews.

OBJECTIVE: Systematic reviews are an appraised method to summarize research in a concise and transparent way, and may enable to draw conclusions beyond the sum of results of individual studies. We assessed the results, quality and external validity of systematic reviews on diet in patients with type 2 diabetes. DESIGN, SETTING, SUBJECTS: We systematically searched for systematic reviews on nutritional interventions in patients with type 2 diabetes that used a reproducible search strategy in at least one major database that applied some form of quality assessment. We assessed quality and the external validity of the retrieved systematic reviews. Outcomes were defined as statistical meta-analyses or narrative results using a predefined and reproducible method. RESULTS: Six systematic reviews met the inclusion criteria, investigating dietary interventions in general (n=3), chromium supplementation (n=1), fish-oil (n=1) or herbs and nutrition supplements (n=1). Quality assessment showed minimal/minor flaws in four cases and major/extensive flaws in two cases. All reviews had insufficient data needed to judge external validity. In reviews with minimal/minor flaws, we found beneficial effects of very-low-calorie diets and fish-oil supplements. However, the external validity of these results could not be assessed sufficiently. CONCLUSIONS: Systematic reviews largely failed to produce knowledge beyond the sum of the original studies. Furthermore, judgment of external validity was hampered in most cases owing to missing data. To improve the quality and usefulness of systematic reviews of dietary interventions, we recommend the application of more focused research questions, but with broader inclusion criteria, for example, the use of observational studies. SPONSORSHIP: Internal funding Radboud University Nijmegen Medical Centre.

Alpha-glucosidase inhibitors for people with impaired glucose tolerance or impaired fasting blood glucose.

BACKGROUND: Alpha-glucosidase inhibitors (AGIs) reduce blood glucose levels and may thus prevent type 2 diabetes and cardiovascular disease in patients with impaired glucose tolerance. These possible effects, and the effects on quality of life, plasma lipids and body weight, have never been investigated in a systematic literature review and meta-analysis. OBJECTIVES: To assess the effects of alpha-glucosidase inhibitors in patients with impaired glucose tolerance (IGT) or impaired fasting blood glucose (IFBG), or both. SEARCH STRATEGY: We searched The Cochrane Library (Clinical Trials database, formerly known as CENTRAL), PUBMED, EMBASE, Web of Science, LILACS, databases of ongoing trials, reference lists of relevant reviews, and we contacted experts and manufacturers. Date of last search was February 2006. SELECTION CRITERIA: Randomised controlled trials of at least one-year duration in patients with IGT or IFBG, or both, comparing AGI monotherapy with any other intervention. DATA COLLECTION AND ANALYSIS: Two reviewers read all abstracts, assessed quality and extracted data independently. Discrepancies were resolved by consensus or by the judgement of a third reviewer. MAIN RESULTS: We included five trials (2360 participants), all investigating acarbose, that included patients with IGT or patients 'at increased risk for diabetes' (n = 1). Study duration was one, three (n = 2), five and six years. One study was at low risk of bias and four studies at high risk of bias. Except for the outcome incidence of type 2 diabetes in acarbose versus no treatment (two studies), meta-analyses were not possible. Data from the study at low risk of bias suggests that acarbose decreases the occurrence of type 2 diabetes (NNT = 10), cardiovascular events (NNT = 50, based on 47 events, study not initially powered for this outcome), post-load blood glucose (-0.6 mmol/L, 95% CI -1.0 to -0.3) and body mass index (0.3 kg/m(2), 95% CI -0.1 to -0.5). No statistically significant effects were observed on mortality, other morbidity, glycated haemoglobin, fasting blood glucose, lipids and blood pressure. The effects on the incidence of type 2 diabetes were confirmed in two studies at high risk of bias (OR 0.2, 95% CI 0.1 to 0.6). Adverse effects were mostly of gastro-intestinal origin (OR 3.5, 95% CI 2.7 to 4.4). AUTHORS' CONCLUSIONS: There is evidence that acarbose reduces the incidence of type 2 diabetes in patients with IGT. However, it is unclear whether this should be seen as prevention, delay or masking of diabetes. Acarbose may prevent the occurrence of cardiovascular events, but this finding needs to be confirmed in more studies.

Alpha-glucosidase inhibitors for type 2 diabetes mellitus.

BACKGROUND: Alpha-glucosidase inhibitors such as acarbose or miglitol, have the potential to improve glycemic control in type 2 diabetes mellitus. The true value of these agents, especially in relation to diabetes related mortality and morbidity, has never been investigated in a systematic literature review and meta-analysis. OBJECTIVES: To assess the effects of alpha-glucosidase inhibitors s in patients with type 2 diabetes mellitus. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, reference lists of reviews on the topic of alpha-glucosidase inhibitors and we contacted experts and manufacturers for additional trials. Date of most recent search: December 2003 (Current Contents) and April 2003 (other databases). SELECTION CRITERIA: Randomised controlled trials of at least 12 weeks duration comparing alpha-glucosidase inhibitor monotherapy in patients with type 2 diabetes with any other intervention and that included at least one of the following outcomes: mortality, morbidity, quality of life, glycemic control, lipids, insulin levels, body weight, adverse events. DATA COLLECTION AND ANALYSIS: Two reviewers read all abstracts, assessed quality and extracted data independently. Discrepancies were resolved by consensus or by the judgement of a third reviewer. A statistician checked all extracted data entrance in the database. We attempted to contact all authors for data clarification. MAIN RESULTS: We included 41 trials (8130 participants), 30 investigated acarbose, seven miglitol, one trial voglibose and three trials compared different alpha-glucosidase inhibitors. Study duration was 24 weeks in most cases and only two studies lasted amply longer than one year. We found only few data on mortality, morbidity and quality of life. Acarbose had a clear effect on glycemic control compared to placebo: glycated haemoglobin -0.8% (95% confidence interval -0.9 to -0.7), fasting blood glucose -1.1 mmol/L (95% confidence interval -1.4 to -0.9), post-load blood glucose -2.3 mmol/L (95% confidence interval -2.7 to -1.9). The effect on glycated haemoglobin by acarbose was not dose-dependent. We found a decreasing effect on post-load insulin and no clinically relevant effects on lipids or body weight. Adverse effects were mostly of gastro-intestinal origin and dose dependent. Compared to sulphonylurea, acarbose decreased fasting and post-load insulin levels by -24.8 pmol/L (95% confidence interval -43.3 to -6.3) and -133.2 pmol/L (95% confidence interval -184.5 to -81.8) respectively and acarbose caused more adverse effects. AUTHORS' CONCLUSIONS: It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes. Conversely, they have a significant effect on glycemic control and insulin levels, but no statistically significant effect on lipids and body weight. These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration. Acarbose dosages higher than 50 mg TID offer no additional effect on glycated hemoglobin but more adverse effects instead. Compared to sulphonylurea, alpha-glucosidase inhibitors lower fasting and post-load insulin levels and have an inferior profile regarding glycemic control and adverse effects.

Introduction of diabetes passports involving both patients and professionals to improve hospital outpatient diabetes care.

AIM: To investigate whether a comprehensive strategy involving both patients and professionals, with the introduction of a diabetes passport as a key component, improves diabetes care. METHODS: The first 150 consecutive patients who visited their internist for a diabetes check up at the internal medicine outpatient departments at each of nine Dutch general hospitals were included in this 1 year clustered, randomised, controlled trial. Health care professionals attended an educational meeting about the use and dissemination of the diabetes passport which is a patient held record. They also received aggregated feedback on baseline data and personal feedback. Educational meetings were also organised for patients. Patient files were used in conjunction with questionnaires to determine adherence rates. Data were analysed using multilevel regression analysis. RESULTS: Small but significant changes were found in mean HbA1c levels. In the intervention group, positive health changes for patients were found (-0.3%) when compared to those in the control group (+0.2%). Diastolic blood pressure improved slightly, but no changes were found in systolic blood pressure or cholesterol. Improvements were found with regard to levels of examination of patients' feet and in patient education. CONCLUSIONS: Efforts to improve professional practice involving both professionals and patients led to small improvements in HbA1c and diastolic blood pressure levels. Further study is needed to establish whether a better structured health care delivery, operating in a more supportive environment can enhance these effects.

Assessing the quality of life of adults with chronic respiratory diseases in routine primary care: construction and first validation of the 10-Item Respiratory Illness Questionnaire-monitoring 10 (RIQ-MON10).

BACKGROUND: As doctors' judgements about the burden of a disease often differ from patients' own assessments a manageable method to incorporate the latter into routine care might support patient-centered decision-making. For this purpose we shortened the 55-Item Quality of Life for Respiratory Illness Questionnaire (QoL-RIQ). METHODS: Secondary analyses of the data of 3 controlled studies (n = 328, 502 and 555). PROCEDURES: inter-item correlations, scale distributions, Cronbach's alpha and factor analysis. Dyspnoea, forced expiratory volume in 1 s (FEV1), COOP/WONCA charts, the Medical Research Council-ECCS symptoms questionnaire and the MOS-SF 36 served as criteria to test validity and responsiveness. RESULTS: Item-reduction resulted in a 10-item short form (alpha's 0.87-0.90), consisting of 2 5-item factors: (1) physical and emotional complaints and (2) physical and social limitations. The correlations of the short form with dyspnoea (r from 0.57 to 0.60), the generic health status instruments (r from 0.39 to 0.59) and lung function (r from 0.10 to 0.15) fulfilled the criteria. FURTHER RESULTS: a clinical relevant score difference (> 0.5) between upper and lower quartiles of the convergent instruments, an intraclass correlation between repeated scores in a stable group of 0.82 and a standardised response mean of 0.86 in an improved group of patients. CONCLUSIONS: The short form (RIQ-MON10) maintained the psychometric properties of the original instrument and is promising for assessing quality of life (QoL) during routine primary care visits.

Intensive support to improve clinical decision making in cardiovascular care: a randomised controlled trial in general practice.

OBJECTIVE: To evaluate the effects of feedback reports combined with outreach visits from trained non-physicians on the clinical decision making of general practitioners (GPs) in cardiovascular care. DESIGN: Pragmatic cluster controlled trial with randomisation of practices to support (intervention group) or no special attention (control group); analysis after 2 years. SETTING: 124 general practices in The Netherlands. PARTICIPANTS: 185 GPs. MAIN OUTCOME MEASURES: Compliance rates for 12 evidence-based indicators for the management of patients with hypertension, hypercholesterolaemia, angina pectoris, or heart failure. The evaluation relied on the prospective recording of patient encounters by the participating GPs. RESULTS: The GPs reported 30 101 clinical decisions at baseline and 22 454 decisions after the intervention. A significant improvement was seen for five of the 12 indicators: assessment of risk factors in patients with hypercholesterolaemia (odds ratio 2.04; 95% CI 1.44 to 2.88) or angina pectoris (3.07; 1.08 to 8.79), provision of information and advice to patients with hypercholesterolaemia (1.58, 1.17 to 2.13) or hypertension (1.55, 1.35 to 1.77), and checking for clinical signs of deterioration in patients with heart failure (4.11, 2.17 to 7.77). Single handed practices, non-training practices, and practices with older GPs gained particular benefit from the intervention. CONCLUSIONS: Intensive support from trained non-physicians can alter certain aspects of the clinical decision making of GPs in cardiovascular care. The effect is small and the strategy needs further development.

Self-management of asthma in general practice, asthma control and quality of life: a randomised controlled trial.

BACKGROUND: A study was undertaken to determine the effectiveness of asthma self-management in general practice. METHODS: Nineteen general practices were randomly allocated to usual care (UC) or self-management (SM). Asthma patients were included after confirmation of the GP diagnosis. Follow up was 2 years. Patients kept diary cards and visited the lung function laboratory every 6 months. Outcomes were number of successfully treated weeks, limited activity days, asthma specific quality of life, forced expiratory volume in 1 second (FEV(1)), FEV(1) reversibility, concentration of histamine provoking a fall in FEV(1) of 20% or more (PC(20) histamine), and amount of inhaled steroids. RESULTS: A total of 214 patients were included in the study (104 UC/110 SM; one third of the total asthma population in general practice); 62% were female. The mean percentage of successfully treated weeks per patient in the UC group was 72% (74/103 weeks) compared with 78% (81/105 weeks) in the SM group (p=0.003). The mean number of limited activity days was 1.2 (95% CI 0.5 to 1.9) in the SM group and 3.9 (95% CI 2.5 to 5.4) in the UC group. The estimated increase in asthma quality of life score was 0.10 points per visit in the UC group and 0.21 points per visit in the SM group (p=0.055). FEV(1), FEV(1) reversibility, and PC(20) histamine did not change. There was a saving of 217 puffs of inhaled steroid per patient in favour of the SM group (p<0.05). CONCLUSION: Self-management lowers the burden of illness as perceived by patients with asthma and is at least as effective as the treatment usually provided in Dutch primary care. Self-management is a safe basis for intermittent treatment with inhaled corticosteroids.

Multifaceted support to improve clinical decision making in diabetes care: a randomized controlled trial in general practice.

AIMS: To evaluate the effectiveness of a multifaceted intervention to improve the clinical decision making of general practitioners (GPs) for patients with diabetes. To identify practice characteristics which predict success. METHODS: Cluster randomized controlled trial with 124 practices and 185 GPs in The Netherlands. The intervention group received feedback reports and support from a facilitator; the control group received no special attention. Outcome measures were the compliance rates with evidence-based recommendations pertaining to discussion of body weight control, discussion of problems with medication, blood pressure measurement, foot examination, eye examination, initiating anti-diabetic medication or increasing the dosage in cases of uncontrolled blood glucose, and scheduling a follow-up appointment. RESULTS: The GPs reported on their clinical decision making in 1410 consultations with Type 2 diabetic patients at baseline and 1449 consultations after the intervention period. The intervention resulted in statistically significant improvement for two of the seven outcome measures: foot examination (odds ratio 1.68; 95% confidence interval 1.19-2.39) and eye examination (1.52; 1.07-2.16). Discussion of problems with medication showed a near significant trend towards increased benefit for the intervention group (1.52; 0.99-2.32). Practice characteristics were not found to be related to the success of the intervention. CONCLUSIONS: Feedback reports with support from facilitators appear to increase rates of foot examination and eye examination in general practice. Alternative interventions should be explored to improve the pursuit of metabolic control by GPs.

Detecting patients at a high risk of developing chronic obstructive pulmonary disease in general practice: cross sectional case finding study.

OBJECTIVES: To investigate the effectiveness of case finding of patients at risk of developing chronic obstructive pulmonary disease, whether the method is suitable for use in general practice, how patients should be selected, and the time required. DESIGN: Cross sectional study. SETTING: Two semirural general practices in the Netherlands. PARTICIPANTS: 651 smokers aged 35 to 70 years. MAIN OUTCOME MEASURES: Short standardised questionnaire on bronchial symptoms for current smokers, lung function with a spirometer, and the quality of the spirometric curve. RESULTS: Of the 201 smokers not taking drugs for a pulmonary condition, 169 produced an acceptable curve (fulfilling American Thoracic Society criteria). Of these, 30 (18%, 95% confidence interval 12% to 24%) had a forced expiratory volume in one second (FEV(1)) <80% of predicted. When smokers were preselected on the basis of chronic cough, the proportion with an FEV(1) <80% of predicted increased to 27% (17 of 64; 12% to 38%). Chronic cough was a better predictor of airflow obstruction than other symptoms, such as wheeze and dyspnoea. The presence of two symptoms was a slightly better predictor than cough only (odds ratio 3.02 (1.37 to 6.64) v 2.50 (1.14 to 5.52)). Age was also a good predictor of obstruction; smokers over 60 with cough had a 48% chance of having an obstruction. The mean time needed for spirometry was four minutes. Detecting one smoker with an FEV(1) <80% of predicted cost 5 pound sterling to 10 pound sterling. CONCLUSIONS: Trained practice assistants could check all patients who smoke for chronic obstructive pulmonary disease at little cost to the practice. Cough and age are the most important predictors of the disease. By testing one smoker a day, an average practice could identify one patient at risk a week.

A placebo-controlled clinical trial of regular monotherapy with short-acting and long-acting beta(2)-agonists in allergic asthmatic patients.

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.

Compliance during long-term treatment with fluticasone propionate in subjects with early signs of asthma or chronic obstructive pulmonary disease (COPD): results of the Detection, Intervention, and Monitoring Program of COPD and Asthma (DIMCA) Study.

In a prospective study, we investigated the long-term compliance to fluticasone propionate (FP) by dry powder inhalation (Rotadisk) in subjects with early signs of asthma and chronic obstructive pulmonary disease (COPD) without an established diagnosis. Subjects were selected from a large screening program on early stages of asthma and COPD (Detection, Intervention, and Monitoring Program of COPD and Asthma [DIMCA] program) in the general practice. Forty-eight adult subjects with "early signs of COPD" (slightly increased forced expiratory volume in 1 sec [FEV1] decline of >0.04L/year) and 29 adult subjects with "early signs of asthma" (signs of bronchial hyperresponsiveness or reversibility) participated in a randomized placebo-controlled trial with FP (Flixotide 500 microg daily) versus placebo with a duration of 2 years or 1 year, respectively. Compliance was measured by counting Rotadisks returned. By means of a questionnaire, participants were asked about perceived effects and/or side effects of the trial drug. The mean overall individual compliance rates of 72% (range 7%-102%) in the early COPD trial and 71% (range 8%-99%) in the early asthma trial were maintained throughout the study. Perceived effectiveness (12% of the participants) or side effects (30% of the participants) of the trial drug were not related to compliance. The willingness of patients to use the trial drug in daily practice if efficacy would be proved was statistically significantly related to compliance during the trial (p = 0.017). It was concluded that the compliance rates found were relatively high in patients with symptoms of mild asthma or COPD without an established diagnosis. Conviction of the importance of treatment influenced compliance more positively than perceived (side) effects. These results again emphasize the importance of patient education in establishing early treatment with inhaled corticosteroids.

Perception of respiratory sensation assessed by means of histamine challenge and threshold loading tests.

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.

Measuring breathlessness during histamine challenge: a simple standardized procedure in asthmatic patients.

One of the problems in research on symptom perception during histamine challenge has been the difficulty in finding both a valid and practical parameter of the "perceptiveness" for bronchoconstriction in a subject. The purpose of this study was to validate whether the slope in the linear regression model between stimulus and sensation during histamine challenge is an appropriate index for the "perceptiveness" for bronchoconstriction by comparing it with the classical Stevens' law. One hundred and thirty-four asthmatic patients were included in the study and underwent a bronchial challenge with histamine. The relationship between the change in visual analogue scale (VAS) values and the change in forced expiratory volume in one second (FEV1) as percentage of baseline value was analysed by determining both the exponent n in deltaVAS=k x (%deltaFEV1)n and the slope alpha in deltaVAS=k + alpha(%deltaFEV1). The best-fitting line of both the exponential and the linear regression model were determined by the least-squares method in which the percentage explained variation (R2) was compared. The median value of R2 of the exponential regression line and the linear regression line was 0.76 and 0.83, respectively, and significantly different. The Spearman rank correlation coefficient between exponent n in the exponential model deltaVAS=k x (%deltaFEV1)n and the slope alpha in the linear regression model deltaVAS=k + alpha(%deltaFEV1) was 0.87 (95% confidence interval 0.83-0.91). On the basis of the results, it was concluded that the linear regression coefficient can be used as a valid expression to describe the "perceptiveness" of an asthmatic subject instead of Stevens' power function during histamine challenge.

Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: "Are inhaled corticosteroids able to slow down the decline in lung function (FEV1) in COPD?" METHODS: A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with "asthmatic features" were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 micrograms beclomethasone daily, six with 1600 micrograms budesonide daily, and eight with 800 micrograms beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV1 was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated. RESULTS: No baseline differences were observed (mean age 61 years, mean FEV1 45% predicted). The estimated two year difference in prebronchodilator FEV1 was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV1 showed a difference of +0.039 l/year (95% CI -0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group. CONCLUSIONS: This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV1 during two years of treatment with relatively high daily dosages of inhaled corticosteroids.