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Purpose Primary care COPD guidelines indicate that COPD patients with asthma characteristics should be treated as having asthma. This study aims to describe the prevalence of asthma characteristics in patients with a pulmonologist-confirmed working diagnosis of COPD or ACO. Patients and methods This retrospective cross-sectional study used real-life data (collected between 2007 and 2017) from a Dutch asthma/COPD-service, a structured web-based system in which pulmonologists support general practitioners in their diagnosis of patients with suspicion of obstructive lung disease. The prevalence of asthma characteristics (history of asthma, atopy, symptoms, and reversibility) and blood eosinophil (Eos) counts were assessed in patients with a working diagnosis of COPD or ACO. Results Of the 14,141 patients, ≥40 years in the dataset, 4475 (31.6%) were diagnosed with asthma, 3532 (25.0%) with COPD, and 1276 (9.0%) with ACO. Asthma characteristics were present in 65.6% (n=1956) of the COPD and 90.9% (n=1059) of the ACO patients. Eos counts of ≥ 300 cells per μL were found in 35.7% (n=924) of the COPD patients and 35.3% (n=341) of the ACO patients. Conclusion In this group of COPD and ACO patients remotely diagnosed by pulmonologists, a substantial proportion would be considered to have asthma characteristics according to the guidelines. This may explain the high number of inhaled corticosteroid (ICS) prescriptions found in primary care COPD patients. Prospective studies are necessary to identify patients who may or may not benefit from ICS containing treatment. Hence, personalized care in primary care can be optimized.

Background: Several tools have been created to assist and guide physicians in the selection of the most suitable inhalation treatment for COPD patients. Nevertheless, it is unclear which patient characteristics really influence treatment decisions in daily clinical practice. Aim: To determine the patient characteristics that guide medication advice for primary care COPD patients, using decision tree modelling. Methods: Data from a Dutch asthma/COPD service was used. In this structured system, pulmonologists electronically support GPs in their diagnosis and treatment of patients with suspicion of obstructive lung disease. These data include patient-reported outcomes (Clinical COPD Questionnaire and Asthma Control Questionnaire(ACQ) in every patient) and spirometry outcome measures. The Chi-squared Automatic Interaction Detection method is used to build a decision tree. Results: Of the 1972 patients included in the analysis, 63% were advised to use a long-acting bronchodilator, 33% an ICS containing treatment (ICS) and 4% a short-acting bronchodilator only. GOLD status was used as the first predictor, other predictors were the ACQ, exacerbations and starting age of complaints. The decision tree was able to correctly predict 45% of the ICS, 79% of the long-acting bronchodilator and 0% of the short-acting bronchodilators treatment advises. Conclusions: Understanding pulmonologists’ prescriptions for patients of whom they only see electronic data is very difficult. Nevertheless, the most important characteristic seems to be GOLD status.The medication advice is however partially in line with the treatment recommendations of (inter)national guidelines.

Anna Jetske Baron,1– 3 Bertine MJ Flokstra-de Blok,1,2,4 Ellen van Heijst,2,5 Roland A Riemersma,6 Agnes MM Sonnenschein-van der Voort,7 Esther I Metting,2,6 Janwillem WH Kocks1,2,8 1General Practitioners Research Institute, Groningen, the Netherlands; 2University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the Netherlands; 3Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, Groningen, the Netherlands; 4Department of Pediatric Pulmonology and Pediatric Allergology, University of Groningen, University Medical Center Groningen, Beatrix Children’s Hospital, Groningen, the Netherlands; 5Astma/COPD Dienst, CERTE Laboratories, Groningen, the Netherlands; 6Department of General Practice and Elderly Care Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; 7GlaxoSmithKline, Zeist, the Netherlands; 8Observational and Pragmatic Research Institute, SingaporeCorrespondence: Anna Jetske Baron Email annajetske@gpri.nlPurpose: Primary care COPD guidelines indicate that COPD patients with asthma characteristics should be treated as having asthma. This study aims to describe the prevalence of asthma characteristics in patients with a pulmonologist-confirmed working diagnosis of COPD or ACO.Patients and Methods: This retrospective cross-sectional study used real-life data (collected between 2007 and 2017) from a Dutch asthma/COPD-service, a structured web-based system in which pulmonologists support general practitioners in their diagnosis of patients with suspicion of obstructive lung disease. The prevalence of asthma characteristics (history of asthma, atopy, symptoms, and reversibility) and blood eosinophil (Eos) counts were assessed in patients with a working diagnosis of COPD or ACO.Results: Of the 14,141 patients, ≥ 40 years in the dataset, 4475 (31.6%) were diagnosed with asthma, 3532 (25.0%) with COPD, and 1276 (9.0%) with ACO. Asthma characteristics were present in 65.6% (n=1956) of the COPD and 90.9% (n=1059) of the ACO patients. Eos counts of ≥ 300 cells per μL were found in 35.7% (n=924) of the COPD patients and 35.3% (n=341) of the ACO patients.Conclusion: In this group of COPD and ACO patients remotely diagnosed by pulmonologists, a substantial proportion would be considered to have asthma characteristics according to the guidelines. This may explain the high number of inhaled corticosteroid (ICS) prescriptions found in primary care COPD patients. Prospective studies are necessary to identify patients who may or may not benefit from ICS containing treatment. Hence, personalized care in primary care can be optimized.Keywords: chronic obstructive pulmonary disease, asthma COPD overlap, asthma characteristics, guidelines

In the Netherlands around 50% of primary care COPD patients use inhaled corticosteroids (ICS), 30% of these probably have no appropriate indication Aim is 10% reduction in ICS (+-LABA) prescriptions for COPD patients A controlled pre/post intervention study with an incomplete control group (media-exposure). The intervention consisted of 1. Education within the regular “Pharmacotherapy meeting” between GP’s and pharmacists, 2. Providing GP’s with a flow chart to decide if the patient could safely stop their ICS, 3. Providing GP’s with a list of patients that might be suitable for de-implementation (patients>55 years who used ICS and had not received courses of predniso(lo)ne in the last year). Medication prescription data was gathered (all patients >55 years who received >2 prescriptions for copd/astma in the preceding 12 months). ICS (+/-LABA), LABA/LAMA, predniso(lo)ne, antibiotics and topical antimycotics were obtained before and after intervention. Intervention group data were compared to the rest of the country There was a significant decrease (11.4%) in ICS – ICS/LABA prescriptions in the whole group, however without significant differences between intervention and control group. See table 1 The 11.4% decrease in ICS prescriptions seems to be a national trend. Active de-implementation can play a role in promoting this. Decrease in ICS in COPD patients use does not seem to be accompanied by an increase in exacerbations

The use of inhaled corticosteroids (ICS) is only indicated for COPD patients with over 2 exacerbations per year and comorbid asthma. Overprescription of ICS is common in Dutch COPD patients. To identify reasons to start and to stop ICS treatment in COPD and to identify barriers and facilitators in the deimplementation process. Sixteen healthcare providers participated in 3 focusgroups (32% general practitioners, 12% nurses, 6% pulmonologists and 50% pharmacists). Sixteen patients participated in 3 focusgroups (mean age 67, 48% male). The focusgroups were semi-structured, audio-recorded, transcibed verbatim and analyzed using grounded theory. The analysis was repeated by a second researcher. Analyses were combined into coding trees. Health care providers gave insight into reasons for starting and stopping ICS treatment (Fig 1). Patients and health care providers suggested facilitators and barriers for deimplementation (Fig 2). Identified themes may guide care givers in the deimplementation of unnecessary ICS use in primary care COPD patients.

BackgroundGenomewide association studies (GWASs) of asthma have identified single-nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR.MethodsA GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data.ResultsA total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta-analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma-associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature.ConclusionsCombining GWAS with subsequent lung eQTL analysis revealed disease-associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma.

BACKGROUND: The management of asthma has changed since the introduction of budesonide/formoterol (Symbicort(®)) as both maintenance and reliever therapy (SMART). SMART and its effects on bronchial hyperresponsiveness (BHR) have not been studied in primary care. AIMS: To compare the effects of SMART and guideline-driven usual care (UC) on BHR and clinical asthma severity in primary care practice. METHODS: Patients with mild-to-moderate stable asthma were randomised to receive SMART treatment (n=54) (budesonide/formoterol 80/4.5μg Turbuhaler(®), two puffs once daily and extra inhalations as needed) or UC treatment (n=48) for 12 months. Diary data, Asthma Control Questionnaire scores, forced expiratory volume in 1 second (FEV(1)), and peak expiratory flow (PEF) measurements were collected during run-in and after 1, 3, 6, and 12 months of treatment. BHR, measured as the dose of histamine provoking a fall in FEV(1) of 20% (PD(20)-histamine), was determined at randomisation and after 12 months. RESULTS: One hundred and two patients with asthma participated in the study. The change in PD20-histamine during the study was not significantly different between the SMART and UC groups (p=0.26). The mean inhaled corticosteroid (ICS) dose was 326μg beclomethasone dipropionate (BDP) equivalents/day (95% CI 254 to 399) with SMART, which was significantly lower (p

INTRODUCTION: Bronchial hyperresponsiveness (BHR) is a hallmark of asthma. Treatment approaches based on BHR severity have been shown to be effective. However, challenge tests are expensive, inconvenient to patients, time consuming, and not easily accessible to general practitioners. Assessment of BHR by a questionnaire would be advantageous in the diagnosis and management of asthma.AIM: To select a set of respiratory symptoms and provoking stimuli related to BHR to compose a reliable Bronchial Hyperresponsiveness Questionnaire (BHQ).METHOD: A list of 33 symptoms and 68 stimuli were selected by in-depth interviews, focus group discussions with asthma patients, and literature review. After a histamine challenge test patients (n=302) were asked to score each question on a 7-point scale (0=no; 6=severe complaints). Factor analysis was performed to identify clusters of interrelated symptoms associated with PC20-histamine. The sensitivity to detect the presence of BHR was analysed by Receiver Operating Curves (ROC). The correlation between the PC20-score and the scores on the questions was analysed.RESULTS: 15 symptoms and 19 provoking stimuli were ultimately selected for the BHQ.CONCLUSION: The BHQ was developed according to FDA-approved standards and is a condition-specific questionnaire able to assess the presence of BHR.

Background: Hypoxemic patients with Chronic Obstructive Pulmonary Disease (COPD) have impaired cognitive performance. These neuropsychological impairments are related to the degree of hypoxemia. So far, cognitive performance has not been tested in non-hypoxemic patients with COPD.Methods: We recruited patients with stable COPD and PaO2 > 8.0 kPa (60 mmHg), as well as healthy subjects, who were matched for age, intelligence quotient (IQ), and level of education. Cognitive performance was studied by Stroop Colour Word Test, Trailmaking, digit-symbol of the Wechsler Adult Intelligence Scale, addition subtest of the Groningen Intelligence Test, and Story Recall.Results: Thirty patients with COPD (FEV1 49.8% pred, mean age 64.8 yr) and 20 healthy volunteers (65.6 yr) were enrolled. COPD patients performed significantly worse on trailmaking B, the digit-symbol test, and on the addition subtest. There was no significant correlation between the tests of cognitive performance and disease specific health status (Chronic Respiratory Questionnaire).Conclusions: We conclude that even non-hypoxemic patients with COPD show significant impairments in cognitive performance. These impairments are not associated with deteriorations in health related quality of life. Prospective evaluation of the impact of treatment on cognitive performance in non-hypoxemic patients with COPD would be a logical subsequent study. (C) 2003 Elsevier Ltd. All rights reserved.

To the Editor: Bronchial hyperresponsiveness (BHR), i.e. increased narrowing of the airways after exposure to non-allergic stimuli, is a hallmark of asthma. BHR is a risk factor for asthma development and, additionally, a marker of worse disease outcome in asthma [1, 2]. It is generally acknowledged that obstruction of the large airways due to inflammation and remodelling contributes to more severe BHR. This is plausible, given that BHR is expressed as the concentration or dose of a stimulus that induces a 20% fall in forced expiratory volume in 1 s (FEV1). Recent studies suggest that asthmatics with BHR have more severe small airways obstruction [3, 4]. However, little is known about the converse, i.e. the association between small airways obstruction and the severity of BHR. Our aim was to assess: 1) whether asthma patients with small airways obstruction express more severe BHR than those without small airways obstruction; and 2) whether small airways obstruction is associated with more severe BHR independently of FEV1. We analysed data from patients with mild-to-moderate asthma who were included in a previously published study on inhaled corticosteroids (ICS) in primary care [5]. All subjects underwent spirometry before and after 1 mg terbutaline, measuring FEV1, forced vital capacity (FVC) and mean expiratory flow at 50% of FVC (MEF50). BHR was assessed using a histamine challenge test, measuring the provocative dose causing a 20% fall in FEV1 (PD20) (histamine). All patients were hyperresponsive to histamine (PD …

BACKGROUND: In 2007, an Asthma/chronic obstructive pulmonary disease (COPD) (AC) service was implemented in the North of the Netherlands to support General Practitioners (GPs) by providing advice from pulmonologists on a systematic basis.AIMS: To evaluate the feasibility and effectiveness of this service on patient-related outcomes.METHODS: We report baseline data on 11,401 patients and follow-up data from 2,556 patients. GPs can refer all patients with possible obstructive airway disease (OAD) to the service, which is conducted by the local laboratory. Patients are assessed in the laboratory using questionnaires and spirometry. Pulmonologists inspect the data through the internet and send the GP diagnosis and management advice.RESULTS: A total of 11,401 patients were assessed by the service, covering almost 60% of all adult patients with projected asthma or COPD in the area. In all, 46% (n = 5,268) of the patients were diagnosed with asthma, 18% (n = 2,019) with COPD and 7% (n = 788) with the overlap syndrome. A total of 740 (7%) patients were followed up after 3 months because the GP advised them to change medication. In this group, the proportion of unstable COPD patients (Clinical COPD Questionnaire (CCQ) >= 1) decreased from 63% (n = 92) at baseline to 49% (n = 72). The proportion of patients with uncontrolled asthma (Asthma Control Questionnaire (ACQ) >= 1.5) decreased from 41% (n = 204) to 23% (n = 115). In all, 938 (8%) patients were followed up after 12 months. From these patients, the proportion of unstable COPD patients (CCQ >= 1) decreased from 47% (n = 115) to 44% (n = 107). The proportion of patients with uncontrolled asthma (ACQ >= 1.5) decreased from 16% (n = 95) to 14% (n = 85).CONCLUSION: The AC service assessed a considerable proportion of patients with OAD in the area, improved patients' outcomes, and is considered to be feasible and effective.

The Control of Allergic Rhinitis and Asthma Test (CARAT) monitors control of asthma and allergic rhinitis. To determine the CARAT’s minimal clinically important difference (MCID) and to evaluate the psychometric properties of the Dutch CARAT. CARAT was applied in three measurements at 1-month intervals. Patients diagnosed with asthma and/or rhinitis were approached. MCID was evaluated using Global Rating of Change (GRC) and standard error of measurement (s.e.m.). Cronbach’s alpha was used to evaluate internal consistency. Spearman’s correlation coefficients were calculated between CARAT, the Asthma Control Questionnaire (ACQ5) and the Visual Analog Scale (VAS) on airway symptoms to determine construct and longitudinal validity. Test–retest reliability was evaluated with intra-class correlation coefficient (ICC). Changes in pollen counts were compared with delta CARAT and ACQ5 scores. A total of 92 patients were included. The MCID of the CARAT was 3.50 based on GRC scores; the s.e.m. was 2.83. Cronbach’s alpha was 0.82. Correlation coefficients between CARAT and ACQ5 and VAS questions ranged from 0.64 to 0.76 (P

Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background (“Dutch hypothesis”).We investigated whether asthma and COPD have common underlying genetic factors, performing genome-wide association studies for both asthma and COPD and combining the results in meta-analyses.Three loci showed potential involvement in both diseases: chr2p24.3, chr5q23.1 and chr13q14.2, containing DDX1, COMMD10 (both participating in the nuclear factor (NF) κβ pathway) and GNG5P5, respectively. Single nucleotide polymorphisms (SNPs) rs9534578 in GNG5P5 reached genome-wide significance after first replication phase (p=9.96×10−9). The second replication phase, in seven independent cohorts, provided no significant replication. Expression quantitative trait loci (eQTL) analysis in blood cells and lung tissue on the top 20 associated SNPs identified two SNPs in COMMD10 that influenced gene expression.Inflammatory processes differ in asthma and COPD and are mediated by NF-κβ, which could be driven by the same underlying genes, COMMD10 and DDX1. None of the SNPs reached genome-wide significance. Our eQTL studies support a functional role for two COMMD10 SNPs, since they influence gene expression in both blood cells and lung tissue. Our findings suggest that there is either no common genetic component in asthma and COPD or, alternatively, different environmental factors, e.g. lifestyle and occupation in different countries and continents, which may have obscured the genetic common contribution.

BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.

Introduction: In budesonide/formoterol (Symbicort (R) Turbuhaler (R), AstraZeneca, Lund, Sweden) maintenance and reliever therapy ( SMART), patients with asthma take a daily maintenance dose of budesonide/formoterol, with the option of taking additional doses for symptom relief instead of a short-acting beta(2)-agonist ( SABA). This study assesses the cost-effectiveness of SMART compared with usual care in patients with mild-to-moderate persistent asthma treated by general practitioners in the Netherlands from a societal perspective. Methods: The study was linked to a randomized, active-controlled, open-label, multicenter, 12-month clinical trial, with a prospective collection of resource use. One hundred and two patients >= 18 years with mild-to-moderate persistent asthma and daily inhaled corticosteroids (ICS) prior to the trial were included. SMART was given as two inhalations of budesonide/formoterol (100/6 mu g) once daily, plus additional doses as needed. The control group was treated according to guidelines, which prescribe medium daily doses of ICS plus an SABA if needed. A long-acting beta(2)-agonist (LABA) is added if necessary. Effectiveness was measured as the proportion of asthma-control days, Asthma Control Questionnaire (ACQ) scores, the net proportion of patients with relevant ACQ improvement, and the proportion of well-controlled patients. Costs included asthma medication, physician contacts, and absence from work. Results: Mean total costs for SMART were (sic)134.81 lower (95% CI: -(sic)439.48; (sic)44.85). Production losses were (sic)94.10 ( 95% CI: -(sic)300.60; (sic)0.29) lower for SMART ((sic)10.77 vs. (sic)104.87). No significant differences in health outcomes were seen, with 3.81 fewer asthma-control days per patient-year for SMART (95% CI: -36.8; 30.8), a 0.049 better ACQ score (95% CI: -0.21; 0.29), a 5.8% larger net proportion of improved patients (95% CI: -15.6%; 27.3%), and a 2.1% (95% CI: -25.5; 20.8%) smaller increase in the proportion of well-controlled patients. Conclusions: Treating primary care patients with mild-to-moderate persistent asthma with SMART instead of ICS plus bronchodilators does not affect health outcomes and does not increase costs; therefore, is likely to be an alternative for guideline-directed treatment, from a health and economic perspective.

INTRODUCTION: Assessment by the general practitioner of the presence, the severity or even the changes in time of BHR by a questionnaire would be an advantage in diagnosing and monitoring patients with asthma. AIMS AND OBJECTIVES: The aim of the study is to select a reliable set of respiratory symptoms and stimuli for the preliminary version of the Bronchial Hyperresponsiveness Questionnaire (BHQ). Subjects and method: A preliminary list of 33 symptoms and 64 stimuli was composed by review of literature, in depth interviews and focus group discussions with asthma patients. After a histamine challenge test patients (n= 302) were asked to score each item on a 7-point Likert scale (0 = no; 6=severe complaints). The questionnaires of patients with a positive challenge test (n = 225) were selected for factor and ROC analysis. A Spearman's rank correlation test was performed to investigate the relation between the PC20-histamine and the scores on the questions in the group of patients with doctors diagnosed asthma (n= 181). An expert panel was asked to define criteria for the selection of suitable questions for the BHQ. Selection criteria were: a significant correlation coefficient of =0.20 and/or a significant positive ROC-analysis. RESULTS: 34 symptoms and stimuli showing a relation with the PC20 were selected for the BHQ. Conclusion/discussion: The symptoms and stimuli correlating best with the PC20 may give an indication of the severity of BHR whereas symptoms and stimuli with significantly ROC-scores are probably sensitive for detecting the presence of BHR. To support this hypothesis further (validation) studies are necessary. Conflict of interest and funding Supported by an unrestricted grant from AstraZeneca BV, The Netherlands.

INTRODUCTION: The severity of BHR in asthmatics is a useful parameter to adjust the dose of inhaled corticosteroids (Sont et al., AmJRCCM 1999). Therefore BHR needs to be assessed repeatedly, using challenge tests. These tests are expensive, time consuming and unpleasant for patients. A questionnaire, specifically designed to assess BHR, could be an alternative. The aim of this study was to generate a list of possible items for such a questionnaire. METHODS: Item-generation was done by extensive review of literature, 11 interviews and a focusgroup discussion with asthmatic patients on symptoms and stimuli, related to BHR. RESULTS: From available asthma questionnaires, few individual items showed correlation's with the severity of BHR. The interviews and the group discussion yielded a set of 30 symptoms and 68 stimuli (table 1). Symptoms Stimuli Sneeze 66 Smoky places 84 Acute tightness of the chest 66 Respiratory infections 75 Inability to breathe deeply 58 Fog 66 Chest tightness 100 Dusty places 92 Cough 66 Exercise 84 Shortness of breath 66 Change from warm to cold 66 Tight belt around chest 50 Grass, pollen 66 Wheeze 75 Tobacco smoke 84 Headache 66 Cold air 75 Irritated mucous membranes 58 Fireplaces 66 Fatigue 50 Chlorine 66 Table 1. Symptoms and stimuli, as mentioned by patients with percentage of patients who mentioned the item. CONCLUSION: In this qualitative study, a variety of symptoms and stimuli that patients relate to BHR were identified. By item reduction, a subset that relates to BHR will be selected. In the future its usefulness in monitoring asthma control will be tested. FUNDING: This study was supported by AstraZeneca, The Netherlands