Budesonide/formoterol maintenance and reliever therapy versus fluticasone/salmeterol fixed-dose treatment in patients with COPD.

BACKGROUND: Maintenance and reliever therapy (MART) with inhaled corticosteroid (ICS)/formoterol effectively reduces exacerbations in asthma. We aimed to investigate its efficacy compared with fixed-dose fluticasone/salmeterol in chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD and ≥1 exacerbation in the previous 2 years were randomly assigned to open-label MART (Spiromax budesonide/formoterol 160/4.5 µg 2 inhalations twice daily+1 prn) or fixed-dose therapy (Diskus fluticasone propionate/salmeterol combination (FSC) 500/50 µg 1 inhalation twice daily+salbutamol 100 µg prn) for 1 year. The primary outcome was rate of moderate/severe exacerbations, defined by treatment with oral prednisolone and/or antibiotics. RESULTS: In total, 195 patients were randomised (MART Bud/Form n=103; fixed-dose FSC n=92). No significant difference was seen between MART and FSC therapy in exacerbation rates (1.32 vs 1.32 /year, respectively, rate ratio 1.05 (95% CI 0.79 to 1.39); p=0.741). No differences in lung function parameters or health status were observed. Total ICS dose was significantly lower with MART than FSC therapy (budesonide-equivalent 928 µg/day vs 1747 µg/day, respectively, p<0.05). Similar proportions of patients reported adverse events (MART Bud/Form: 73% vs fixed-dose FSC: 68%, p=0.408) and pneumonias (MART: 5% vs FSC: 1%, p=0.216). CONCLUSIONS: This first study of MART in COPD found that budesonide/formoterol MART might be similarly effective to fluticasone/salmeterol fixed-dose therapy in moderate to severe patients with COPD, at a lower daily ICS dosage. Further evidence is needed about long-term safety.

Development of a tool to detect small airways dysfunction in asthma clinical practice.

BACKGROUND: Small airways dysfunction (SAD) in asthma is difficult to measure and a gold standard is lacking. The aim of this study was to develop a simple tool including items of the Small Airways Dysfunction Tool (SADT) questionnaire, basic patient characteristics and respiratory tests available depending on the clinical setting to predict SAD in asthma. METHODS: This study was based on the data of the multinational ATLANTIS (Assessment of Small Airways Involvement in Asthma) study including the earlier developed SADT questionnaire. Key SADT items together with clinical information were now used to build logistic regression models to predict SAD group (less likely or more likely to have SAD). Diagnostic ability of the models was expressed as area under the receiver operating characteristic curve (AUC) and positive likelihood ratio (LR+). RESULTS: SADT item 8, "I sometimes wheeze when I am sitting or lying quietly", and the patient characteristics age, age at asthma diagnosis and body mass index could reasonably well detect SAD (AUC 0.74, LR+ 2.3). The diagnostic ability increased by adding spirometry (percentage predicted forced expiratory volume in 1 s: AUC 0.87, LR+ 5.0) and oscillometry (resistance difference between 5 and 20 Hz and reactance area: AUC 0.96, LR+ 12.8). CONCLUSIONS: If access to respiratory tests is limited (e.g. primary care in many countries), patients with SAD could reasonably well be identified by asking about wheezing at rest and a few patient characteristics. In (advanced) hospital settings patients with SAD could be identified with considerably higher accuracy using spirometry and oscillometry.

Identifying critical inhalation technique errors in Dry Powder Inhaler use in patients with COPD based on the association with health status and exacerbations: findings from the multi-country cross-sectional observational PIFotal study.

BACKGROUND: Correct inhaler use depends on a complex interplay of factors, including device preparation and generating sufficient inspiratory flow. It is currently unknown which inhalation technique errors can be considered critical in Chronic Obstructive Pulmonary Disease (COPD) patients on Dry Powder Inhaler (DPI) maintenance therapy. OBJECTIVE: To investigate the association between inhalation technique errors and health status or exacerbations in patients with COPD. Additionally, the association between the number of errors and COPD outcomes was determined. METHODS: The PIFotal study is a cross-sectional multi-country observational study in a primary care setting, including 1434 COPD patients aged ≥ 40 years (50.1% female; mean age 69.2 yrs) using a DPI for their maintenance therapy. Inhalation technique was video recorded and scored by two independent researchers using inhaler-specific checklists. Health status was assessed with two questionnaires; the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT). The number of moderate and severe exacerbations in the past 12 months was recorded. Critical errors were identified based on their association with health status or exacerbations through multi-level prediction models adjusted for identified confounding. RESULTS: Errors in inhalation technique steps 'Breathe in', 'Hold breath', and 'Breathe out calmly after inhalation' were significantly associated with poorer CCQ and CAT outcomes and thus deemed critical. None of the errors were significantly associated with moderate exacerbations. Patients with errors 'Preparation', 'Hold inhaler in correct position during inhalation', and 'Breathe in' had significantly more severe exacerbations, and therefore these errors were also deemed critical. 81.3% of patients with COPD made at least one critical error. Specific combinations of errors were associated with worse outcomes. The more inhalation technique errors identified, the poorer the health status and the higher the exacerbation rate. CONCLUSION: In this study, we identified multiple critical inhalation technique errors in COPD patients using DPIs each associated with poorer outcomes. Explorative analysis revealed that specific combinations of errors may be of clinical relevance, especially those related to the inhalation manoeuvre. COPD outcomes worsened with increasing error count. These results warrant further prospective longitudinal studies to establish the effect of correcting these errors on COPD control. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04532853 (31/08/2020).

The Use of eHealth for Pharmacotherapy Management With Patients With Respiratory Disease, Cardiovascular Disease, or Diabetes: Scoping Review.

BACKGROUND: eHealth is increasingly considered an important tool for supporting pharmacotherapy management. OBJECTIVE: We aimed to assess the (1) use of eHealth in pharmacotherapy management with patients with asthma or chronic obstructive pulmonary disease (COPD), diabetes, or cardiovascular disease (CVD); (2) effectiveness of these interventions on pharmacotherapy management and clinical outcomes; and (3) key factors contributing to the success of eHealth interventions for pharmacotherapy management. METHODS: We conducted a scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review) statement. Databases searched included Embase, MEDLINE (PubMed), and Cochrane Library. Screening was conducted by 2 independent researchers. Eligible articles were randomized controlled trials and cohort studies assessing the effect of an eHealth intervention for pharmacotherapy management compared with usual care on pharmacotherapy management or clinical outcomes in patients with asthma or COPD, CVD, or diabetes. The interventions were categorized by the type of device, pharmacotherapy management, mode of delivery, features, and domains described in the conceptual model for eHealth by Shaw at al (Health in our Hands, Interacting for Health, Data Enabling Health). The effectiveness on pharmacotherapy management outcomes and patient- and clinician-reported clinical outcomes was analyzed per type of intervention categorized by number of domains and features to identify trends. RESULTS: Of 63 studies, 16 (25%), 31 (49%), 13 (21%), and 3 (5%) included patients with asthma or COPD, CVD, diabetes, or CVD and diabetes, respectively. Most (38/63, 60%) interventions targeted improving medication adherence, often combined for treatment plan optimization. Of the 16 asthma or COPD interventions, 6 aimed to improve inhaled medication use. The majority (48/63, 76%) of the studies provided an option for patient feedback. Most (20/63, 32%) eHealth interventions combined all 3 domains by Shaw et al, while 25% (16/63) combined Interacting for Health with Data Enabling Health. Two-thirds (42/63, 67%) of the studies showed a positive overall effect. Respectively, 48% (23/48), 57% (28/49), and 39% (12/31) reported a positive effect on pharmacotherapy management and clinician- and patient-reported clinical outcomes. Pharmacotherapy management and patient-reported clinical outcomes, but not clinician-reported clinical outcomes, were more often positive in interventions with ≥3 features. There was a trend toward more studies reporting a positive effect on all 3 outcomes with more domains by Shaw et al. Of the studies with interventions providing patient feedback, more showed a positive clinical outcome, compared with studies with interventions without feedback. This effect was not seen for pharmacotherapy management outcomes. CONCLUSIONS: There is a wide variety of eHealth interventions combining various domains and features to target pharmacotherapy management in asthma or COPD, CVD, and diabetes. Results suggest feedback is key for a positive effect on clinician-reported clinical outcomes. eHealth interventions become more impactful when combining domains.

European Respiratory Society Guidelines for the Diagnosis of Asthma in Adults.

Although asthma is very common affecting 5-10% of the population, the diagnosis of asthma in adults remains a challenge in the real world that results in both over- and under-diagnosis. A task force (TF) was set up by the European Respiratory Society to systematically review the literature on the diagnostic accuracy of tests used to diagnose asthma in adult patients and provide recommendation for clinical practice.The TF defined eight PICO (Population, Index, Comparator, and Outcome) questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach, The TF utilised the outcomes to develop an evidenced-based diagnostic algorithm, with recommendations for a pragmatic guideline for everyday practice that was directed by real-life patient experiences.The TF support the initial use of spirometry followed, and if airway obstruction is present, by bronchodilator reversibility testing. If initial spirometry fails to show obstruction, further tests should be performed in the following order: FeNO, PEF variability or in secondary care, bronchial challenge. We present the thresholds for each test that are compatible with a diagnosis of asthma in the presence of current symptoms.The TF reinforce the priority to undertake spirometry and recognise the value of measuring blood eosinophils and serum IgE to phenotype the patient. Measuring gas trapping by body plethysmography in patients with preserved FEV1/FVC ratio deserves further attention. The TF draw attention on the difficulty of making a correct diagnosis in patients already receiving inhaled corticosteroids, the comorbidities that may obscure the diagnosis, the importance of phenotyping, and the necessity to consider the patient experience in the diagnostic process.

Pharmacology, particle deposition and drug administration techniques of intranasal corticosteroids for treating allergic rhinitis.

This review presents an overview of the available literature regarding intranasal corticosteroids (INCs) for the treatment of allergic rhinitis (AR). Various treatment options exist for AR including INCs, antihistamines and leucotriene antagonists. INCs are considered to be the most effective therapy for moderate-to-severe AR, as they are effective against nasal and ocular symptoms and improve quality of life. Their safety has been widely observed. INCs are effective and safe for short-term use. Local adverse events are observed but generally well-tolerated. The occurrence of (serious) systemic adverse events is unlikely but cannot be ruled out. There is a lack of long-term safety data. INC may cause serious eye complications. The risk of INCs on the hypothalamic-pituitary-adrenal axis, on bone mineral density reduction or osteoporosis and on growth in children, should be considered during treatment. Pharmacological characteristics of INCs (e.g. the mode of action and pharmacokinetics) are well known and described. We sought to gain insight into whether specific properties affect the efficacy and safety of INCs, including nasal particle deposition, which the administration technique affects. However, advances are lacking regarding the improved understanding of the effect of particle deposition on efficacy and safety and the effect of the administration technique. This review emphasizes the gaps in knowledge regarding this subject. Advances in research and health care are necessary to improve care for patients with AR.

Allergic and hypersensitivity conditions in non-specialist care: Flow diagrams to support clinical practice.

Most patients presenting with allergies are first seen by primary care health professionals. The perceived knowledge gaps and educational needs were recently assessed in response to which the LOGOGRAM Task Force was established with the remit of constructing pragmatic flow diagrams for common allergic conditions in line with an earlier EAACI proposal to develop simplified pathways for the diagnosis and management of allergic diseases in primary care. To address the lack of accessible and pragmatic guidance, we designed flow diagrams for five major clinical allergy conditions: asthma, anaphylaxis, food allergy, drug allergy, and urticaria. Existing established allergy guidelines were collected and iteratively distilled to produce five pragmatic and accessible tools to aid diagnosis and management of these common allergic problems. Ultimately, they should now be validated prospectively in primary care settings.

COPD Population in US Primary Care: Data From the Optimum Patient Care DARTNet Research Database and the Advancing the Patient Experience in COPD Registry.

PURPOSE: To describe demographic and clinical characteristics of chronic obstructive pulmonary disease patients managed in US primary care. METHODS: This was an observational registry study using data from the Chronic Obstructive Pulmonary Disease (COPD) Optimum Patient Care DARTNet Research Database from which the Advancing the Patient Experience COPD registry is derived. Registry patients were aged ≥35 years at diagnosis. Electronic health record data were collected from both registries, supplemented with patient-reported information/outcomes from the Advancing the Patient Experience registry from 5 primary care groups in Texas, Ohio, Colorado, New York, and North Carolina (June 2019 through November 2020). RESULTS: Of 17,192 patients included, 1,354 were also in the Advancing the Patient Experience registry. Patients were predominantly female (56%; 9,689/17,192), White (64%; 9,732/15,225), current/ex-smokers (80%; 13,784/17,192), and overweight/obese (69%; 11,628/16,849). The most commonly prescribed maintenance treatments were inhaled corticosteroid with a long-acting ß2-agonist (30%) and inhaled corticosteroid with a long-acting muscarinic antagonist (27%). Although 3% (565/17,192) of patitents were untreated, 9% (1,587/17,192) were on short-acting bronchodilator monotherapy, and 4% (756/17,192) were on inhaled corticosteroid monotherapy. Despite treatment, 38% (6,579/17,192) of patients experienced 1 or more exacerbations in the last 12 months. These findings were mirrored in the Advancing Patient Experience registry with many patients reporting high or very high impact of disease on their health (43%; 580/1,322), a breathlessness score 2 or more (45%; 588/1,315), and 1 or more exacerbation in the last 12 months (50%; 646/1,294). CONCLUSIONS: Our findings highlight the high exacerbation, symptom, and treatment burdens experienced by COPD patients managed in US primary care, and the need for more real-life effectiveness trials to support decision making at the primary care level.

Expert Statement: Pneumothorax Associated with One-Way Valve Therapy for Emphysema: 2020 Update.

For selected patients with advanced emphysema, bronchoscopic lung volume reduction with one-way valves can lead to clinically relevant improvements of airflow obstruction, hyperinflation, exercise capacity, and quality of life. The most common complication of this procedure is pneumothorax with a prevalence of up to ±34% of the treated patients. Patients who develop a pneumothorax also experience meaningful clinical benefits once the pneumothorax is resolved. Timely resolution of a post-valve treatment pneumothorax requires skilled and adequate pneumothorax management. This expert panel statement is an updated recommendation of the 2014 statement developed to help guide pneumothorax management after valve placement. Additionally, mechanisms for pneumothorax development, risk assessment, prevention of pneumothorax, and outcomes after pneumothorax are addressed. This recommendation is based on a combination of the current scientific literature and expert opinion, which was obtained through a modified Delphi method.

An expert consensus framework for asthma remission as a treatment goal.

With novel therapies in development, there is an opportunity to consider asthma remission as a treatment goal. In this Rostrum, we present a generalized framework for clinical and complete remission in asthma, on and off treatment, developed on the basis of medical literature and expert consensus. A modified Delphi survey approach was used to ascertain expert consensus on core components of asthma remission as a treatment target. Phase 1 identified other chronic inflammatory diseases with remission definitions. Phase 2 evaluated components of those definitions as well as published definitions of spontaneous asthma remission. Phase 3 evaluated a remission framework created using consensus findings. Clinical remission comprised 12 or more months with (1) absence of significant symptoms by validated instrument, (2) lung function optimization/stabilization, (3) patient/provider agreement regarding remission, and (4) no use of systemic corticosteroids. Complete remission was defined as clinical remission plus objective resolution of asthma-related inflammation and, if appropriate, negative bronchial hyperresponsiveness. Remission off treatment required no asthma treatment for 12 or more months. The proposed framework is a first step toward developing asthma remission as a treatment target and should be refined through future research, patient input, and clinical study.

Association between COPD exacerbations and lung function decline during maintenance therapy.

BACKGROUND: Little is known about the impact of exacerbations on COPD progression or whether inhaled corticosteroid (ICS) use and blood eosinophil count (BEC) affect progression. We aimed to assess this in a prospective observational study. METHODS: The study population included patients with mild to moderate COPD, aged ≥35 years, with a smoking history, who were followed up for ≥3 years from first to last spirometry recording using two large UK electronic medical record databases: Clinical Practice Research Datalink (CPRD) and Optimum Patient Care Research Database (OPCRD). Multilevel mixed-effects linear regression models were used to determine the relationship between annual exacerbation rate following initiation of therapy (ICS vs non-ICS) and FEV1 decline. Effect modification by blood eosinophils was studied through interaction terms. RESULTS: Of 12178 patients included (mean age 66 years; 48% female), 8981 (74%) received ICS. In patients with BEC ≥350 cells/µL not on ICS, each exacerbation was associated with subsequent acceleration of FEV1 decline of 19.4 mL/year (95% CI 12.0 to 26.7, p<0.0001). This excess decline was reduced by 15.1 mL/year (6.6 to 23.6) to 4.3 mL/year (1.9 to 6.7, p<0.0001) in those with BEC ≥350 cells/µL treated with ICS. CONCLUSION: Exacerbations are associated with a more rapid loss of lung function among COPD patients with elevated blood eosinophils, defined as ≥350 cells/µL, not treated with ICS. More aggressive prevention of exacerbations using ICS in such patients may prevent excess loss of lung function.

Improving antibacterial prescribing safety in the management of COPD exacerbations: systematic review of observational and clinical studies on potential drug interactions associated with frequently prescribed antibacterials among COPD patients.

BACKGROUND: Guidelines advise the use of antibacterials (ABs) in the management of COPD exacerbations. COPD patients often have multiple comorbidities, such as diabetes mellitus and cardiac diseases, leading to polypharmacy. Consequently, drug-drug interactions (DDIs) may frequently occur, and may cause serious adverse events and treatment failure. OBJECTIVES: (i) To review DDIs related to frequently prescribed ABs among COPD patients from observational and clinical studies. (ii) To improve AB prescribing safety in clinical practice by structuring DDIs according to comorbidities of COPD. METHODS: We conducted a systematic review by searching PubMed and Embase up to 8 February 2018 for clinical trials, cohort and case-control studies reporting DDIs of ABs used for COPD. Study design, subjects, sample size, pharmacological mechanism of DDI and effect of interaction were extracted. We evaluated levels of DDIs and quality of evidence according to established criteria and structured the data by possible comorbidities. RESULTS: In all, 318 articles were eligible for review, describing a wide range of drugs used for comorbidities and their potential DDIs with ABs. DDIs between ABs and co-administered drugs could be subdivided into: (i) co-administered drugs altering the pharmacokinetics of ABs; and (ii) ABs interfering with the pharmacokinetics of co-administered drugs. The DDIs could lead to therapeutic failures or toxicities. CONCLUSIONS: DDIs related to ABs with clinical significance may involve a wide range of indicated drugs to treat comorbidities in COPD. The evidence presented can support (computer-supported) decision-making by health practitioners when prescribing ABs during COPD exacerbations in the case of co-medication.

Wrong inhalation technique is associated to poor asthma clinical outcomes. Is there room for improvement?

PURPOSE OF REVIEW: The long-term goals of asthma management are to control symptoms and to reduce the risk of exacerbations. Inhaled medication is the cornerstone of pharmacological treatment for asthma; therefore, good inhalation technique is the key for asthma management. However, up to 70% of asthma patients do not use their inhalers correctly. There is evidence on how poor inhalation technique is associated to poor asthma control. The purpose of this review is to present the most recent research in this field to help clinicians understand the importance of proper inhalers use and the possible interventions to optimize patients' inhalation technique. RECENT FINDINGS: New evidence on how poor inhaler technique and specific critical errors are significantly associated to poor asthma control and exacerbations and how this negative impact could be improved by optimizing device selection, enhancing shared decision-making and giving more importance to education, both for patients and healthcare professionals. New devices and additional tools might help patients to achieve the correct inhaler technique and could form the basis of simplified educational interventions. SUMMARY: There is an urgent need for specific interventions including new educational strategies to minimize the negative effects of wrong inhalation technique in asthma clinical outcomes.

Economic Impact of Reducing Inappropriate Inhaled Corticosteroids Use in Patients With Chronic Obstructive Pulmonary Disease: ISPOR's Guidance on Budget Impact in Practice.

OBJECTIVES: To assess the budget impact of restricting inappropriate inhaled corticosteroids (ICS) use according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD)-guidelines indication for ICS use in the chronic obstructive pulmonary disease (COPD)-population, taking The Netherlands as a reference case. METHODS: A budget impact model was developed and closely aligned with the International Society for Pharmacoeconomics and Outcomes Research best-practice guidelines. The model estimates the impact of pharmacologic COPD maintenance treatments on clinical events (exacerbations and pneumonias) and associated healthcare utilization and costs. The current treatment mix included all maintenance treatments including long-acting muscarinic antagonists (LAMA), long-acting ß2-agonists (LABA), LABA/ICS, LABA/LAMA, and triple therapy (LABA/LAMA/ICS). We modeled a situation where 25% of patients would use ICS-containing treatments and compared this to the current Dutch situation with 60% ICS use. A 5-year time horizon with a Dutch healthcare payer's perspective was used. In sensitivity analyses, a range of values for absolute ICS reduction (20%-40%), relative risks of exacerbations and pneumonia events, and other input parameters were explored. RESULTS: Over a period of 5 years, the new treatment mix with Global Initiative for Chronic Obstructive Lung Disease guideline recommended ICS, and LABA/LAMA use resulted in potential avoidance of 17 405 exacerbations and 11 984 pneumonias and accompanied savings of €84 million in the base-case scenario. Savings were consistent in various sensitivity analyses, indicating cost savings between €30 and €200 million. CONCLUSION: Reducing inappropriate ICS use and increasing use of LABA/LAMA in COPD patients could result in a reduction of exacerbations and pneumonias, corresponding with a reduction in total costs for COPD in The Netherlands.

Clinically relevant differences in COPD health status: systematic review and triangulation.

The minimal clinically important difference (MCID) quantifies when measured differences can be considered clinically relevant. This study aims to review and triangulate MCIDs of chronic obstructive pulmonary disease (COPD) health status tools.A systematic search in PubMed, EMBASE and Cochrane Library was conducted (Prospero #CRD42015023221). Study details, patient characteristics, MCID methodology and estimates were assessed and extracted by two authors. A triangulated mean was obtained for each tool's MCID, with two-thirds weighting for anchor-based and one-third for distribution-based results. This was then multiplied by a weighted factor based upon the study size and quality rating.Overall, 785 records were reviewed of which 21 studies were included for analysis. MCIDs of 12 tools were presented. General quality and risk of bias were average to good. Triangulated MCIDs for the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and St. George's Respiratory Questionnaire (SGRQ) were -2.54, -0.43 and -7.43 for improvement. Too few and/or too diverse studies were present to triangulate MCIDs of other tools.Evidence for the MCID of the CAT and CCQ was strong and triangulation was valid. Currently used MCIDs in clinical practice for the SGRQ (4) and Chronic Respiratory Questionnaire (0.5) did not match the reviewed content, for which the MCIDs were much higher. Using too low MCIDs may lead to an overestimation of the interpretation of treatment effects. MCIDs for deterioration were scarce, which highlights the need for more research.

Effects of prophylactic antibiotics on patients with stable COPD: a systematic review and meta-analysis of randomized controlled trials.

Background: As bacterial infections provoke exacerbations, COPD patients may benefit from prophylactic antibiotics. However, evidence regarding their overall benefit-risk profile is conflicting. Objectives: To update previous evidence and systematically evaluate the beneficial effects and side effects of prophylactic antibiotics in stable COPD patients. Methods: Several databases were searched up to 26 April 2017 for randomized controlled trials (RCTs) on prophylactic antibiotics in stable COPD patients. The primary outcomes were exacerbations and quality of life. Duration and schedule of antibiotics were considered in subgroup analyses. Results: Twelve RCTs involving 3683 patients were included. Prophylactic antibiotics significantly reduced the frequency of exacerbations [risk ratio (RR) 0.74, 95% CI 0.60-0.92] and the number of patients with one or more exacerbations (RR 0.82, 95% CI 0.74-0.90). Erythromycin and azithromycin appeared the most effective, with the number needed to treat ranging from four to seven. Quality of life was also significantly improved by prophylactic antibiotics (mean difference -1.55, 95% CI -2.59 to -0.51). Time to first exacerbation was prolonged in six studies, with one conflicting result. Neither the rate of hospitalization nor the rate of adverse events was significantly changed. Furthermore, no significant changes were observed in lung function, bacterial load and airway inflammation. However, antibiotic-resistant isolates were significantly increased (OR 4.49, 95% CI 2.48-8.12). Conclusions: Prophylactic antibiotics were effective in preventing COPD exacerbations and improving quality of life among stable patients with moderate to severe COPD. The choice of prophylactic antibiotics should be analysed and considered case by case, especially for long and continuous use.

Assessing patient-reported outcomes in asthma and COPD patients: which can be recommended in clinical practice?

PURPOSE OF REVIEW: There is a clear need for simple and reliable patient-reported outcome measures for chronic obstructive pulmonary disease (COPD) and asthma in daily practice. The purpose of this review is to facilitate the choice for clinicians of patient-reported outcomes which they can use in their daily practice. RECENT FINDINGS: More than 50 patient-reported outcome measures for asthma and COPD exist and clinicians are often left confused on which to use. Four tools (two for asthma and two for COPD) can be suggested based on validity/reliability, responsiveness, practicality and are particularly convenient in terms of time to measure. SUMMARY: On the basis of ample evidence, the COPD assessment test and the clinical COPD questionnaire for COPD and asthma control questionnaire and the asthma control test for asthma can be recommended for use in both primary care and other clinical settings. A simple guide figured as smiley faces has been designed to assist physicians to easily select the appropriate measure. With the current direction of thinking into treatable traits, targeted measures that evaluate the upper airways like the control of allergic rhinitis and asthma test may also be more used in the future.

Associations between chronic comorbidity and exacerbation risk in primary care patients with COPD.

BACKGROUND: COPD often coexists with chronic conditions that may influence disease prognosis. We investigated associations between chronic (co)morbidities and exacerbations in primary care COPD patients. METHOD: Retrospective cohort study based on 2012-2013 electronic health records from 179 Dutch general practices. Comorbidities from patients with physician-diagnosed COPD were categorized according to International Classification of Primary Care (ICPC) codes. Chi-squared tests, uni- and multivariable logistic, and Cox regression analyses were used to study associations with exacerbations, defined as oral corticosteroid prescriptions. RESULTS: Fourteen thousand six hundred three patients with COPD could be studied (mean age 67 (SD 12) years, 53% male) for two years. At baseline 12,826 (88%) suffered from ≥1 comorbidities, 3263 (22%) from ≥5. The most prevalent comorbidities were hypertension (35%), coronary heart disease (19%), and osteoarthritis (18%). Several comorbidities showed statistically significant associations with frequent (i.e., ≥2/year) exacerbations: heart failure (odds ratio [OR], 95% confidence interval: 1.72; 1.38-2.14), blindness & low vision (OR 1.46; 1.21-1.75), pulmonary cancer (OR 1.85; 1.28-2.67), depression 1.48; 1.14-1.91), prostate disorders (OR 1.50; 1.13-1.98), asthma (OR 1.36; 1.11-1.70), osteoporosis (OR 1.41; 1.11-1.80), diabetes (OR 0.80; 0.66-0.97), dyspepsia (OR 1.25; 1.03-1.50), and peripheral vascular disease (OR 1.20; 1.00-1.45). From all comorbidity categories, having another chronic respiratory disease beside COPD showed the highest risk for developing a new exacerbation (Cox hazard ratio 1.26; 1.17-1.36). CONCLUSION: Chronic comorbidities are highly prevalent in primary care COPD patients. Several chronic comorbidities were associated with having frequent exacerbations and increased exacerbation risk.

Mapping the clinical chronic obstructive pulmonary disease questionnaire onto generic preference-based EQ-5D values.

OBJECTIVES: To develop a model to predict EuroQol five-dimensional questionnaire (EQ-5D) values from clinical chronic obstructive pulmonary disease (COPD) questionnaire (CCQ) scores. METHODS: We used data from three clinical trials (the Randomized Clinical Trial on Effectiveness of Integrated COPD Management in Primary Care [RECODE], the Assessment Of Going Home Under Early Assisted Discharge [GO-AHEAD], and the Health Status Guided COPD Care [MARCH]). Data were randomly split into an estimation sample and a validation sample. The conceptual similarity between patient-reported CCQ and preference-based EQ-5D scores was assessed using correlation and principal-component analysis. Different types of models were estimated with increasing complexity. We selected the final models on the basis of mean absolute error and root mean square error when comparing predicted and observed values from the same population (internal validity) and from different trial populations (external validity). We also developed models for different country-specific EQ-5D value sets. RESULTS: The principal-component analysis showed that the CCQ domains functional state and mental state are associated with four dimensions of the EQ-5D. The EQ-5D dimension pain/discomfort formed a separate construct on which no CCQ item loaded. The mean observed EQ-5D values were not significantly different from the mean predicted EQ-5D values in internal validation samples but did significantly differ in external validation samples. The models underestimated EQ-5D values in milder health states and overestimated them in more severe health states. The predictive ability of the models was similar across different EQ-5D value sets. CONCLUSIONS: The models can predict mean EQ-5D values that are similar to observed mean values in a similar population. The overestimating/underestimating of the low/high EQ-5D values, however, limits its use in Markov models. Therefore, mapping should be used cautiously.