Individual trajectory-based care for COPD: getting closer, but not there yet.

Chronic obstructive pulmonary disease (COPD) is a main cause of death due to interplaying factors, including comorbidities that interfere with symptoms and response to therapy. It is now admitted that COPD management should be based on clinical symptoms and health status and should consider the heterogeneity of patients' phenotypes and treatable traits. This precision medicine approach involves a regular assessment of the patient's status and of the expected benefits and risks of therapy. The cornerstone of COPD pharmacological therapy is inhaled long-acting bronchodilation. In patients with persistent or worsened symptoms, factors likely to interfere with treatment efficacy include the patient's non-adherence to therapy, treatment preference, inhaler misuse and/or comorbidities, which should be systematically investigated before escalation is considered. Several comorbidities are known to impact symptoms, physical and social activity and lung function. The possible long-term side-effects of inhaled corticosteroids contrasting with their over-prescription in COPD patients justify the regular assessment of their benefits and risks, and de-escalation under close monitoring after a sufficient period of stability is to be considered. While commonly used in clinical trials, the relevance of routine blood eosinophil counts to guide therapy adjustment is not fully clear. Patients' characteristics, which define phenotypes and treatable traits and thus guide therapy, often change during life, forming the basis of the concept of clinical trajectory. The application of individual trajectory-based management of COPD in clinical practice therefore implies that the benefit:risk ratio is regularly reviewed according to the evolution of the patient's traits over time to allow optimised therapy adjustments.

Tracheobronchial involvement of relapsing polychondritis.

Recent studies show that relapsing polychondritis patients with tracheobronchial involvement are distinct from others in terms of clinical characteristics, therapeutic management, and disease evolution. Tracheobronchial involvement affects 20 to 50% of patients and may reveal the disease. It should be sought at the time of diagnosis and at each follow-up visit. Respiratory impairment is confirmed by computed tomography (CT) of the chest, including the cervical portion of the trachea, with end-inspiratory and dynamic expiratory scans, and pulmonary function tests. These investigations should be performed, even in asymptomatic patients, at the time of diagnosis, and repeated as necessary during follow-up. Bronchoscopy and a fortiori endoscopic intervention should be considered with caution and performed only by expert endoscopists after careful evaluation of the risks and benefits of such procedures, which can lead to damage or perforation of the airways and bronchospasm. Early detection and management of tracheobronchial involvement in relapsing polychondritis has significantly improved the prognosis of patients, especially with the development of interventional fiberoptic bronchoscopy. However, relapsing polychondritis-related morbidity and mortality are still elevated, particularly in tracheobronchial disease.

Safety of tiotropium in patients with asthma.

Given the high proportion of patients with asthma who remain uncontrolled despite controller treatment, there remains a need for the development of more effective treatment options with a proven safety and tolerability profile. Recently, asthma guidelines have evolved to incorporate new therapies, including long-acting muscarinic antagonists (LAMAs) and biologics. Here we focus on the safety profile of tiotropium, a LAMA, using data from the large-scale UniTinA-asthma® clinical trial program, which investigated the use of tiotropium in over 6000 patients with asthma who remained symptomatic despite receiving inhaled corticosteroids (ICS) maintenance therapy, with or without other adjunct therapies. The large number of patients included allows robust analysis of safety and tolerability. Overall, a similar incidence of patients reporting any adverse event (AE) was observed in the tiotropium (5 µg and 2.5 µg) and placebo groups. Asthma worsening, decreased peak expiratory flow, and upper respiratory tract infections were the most frequently reported AEs. Serious AEs (SAEs) and investigator-defined drug-related AEs were infrequently reported across all treatment groups, including the placebo group, and there were no deaths in any study. Reports of side effects typically associated with anticholinergic drugs, such as dry mouth and urinary retention, were either infrequent or not reported in children, adolescents or adults. The similar proportions of tiotropium- versus placebo-treated patients reporting AEs and SAEs in African-American and Japanese populations, as well as in elderly patients, contribute to the accumulating evidence of the safety and tolerability of tiotropium across broad ethnic and age populations.

Postoperative outcomes of frequent exacerbator patients with Chronic Obstructive Pulmonary Disease after resection of Non-Small Cells Lung Cancer.

Chronic obstructive pulmonary disease (COPD) is a risk factor of post-operative complications after lung cancer resection. The influence of the "frequent exacerbator (FE)" phenotype (at least three exacerbations per year) is unknown. Postoperative outcomes of frequent exacerbators (POFE) was a prospective observational study of patients with COPD undergoing lung resection for cancer. The inclusion criteria were: age >40 years, FEV1/FVC <70%, non-urgent surgery for lung cancer, filled out self-questionnaires. The primary outcome was assessment of postoperative pulmonary complications (purulent tracheobronchitis, atelectasis, pneumonia, acute respiratory failure, need of mechanical ventilation). Secondary outcomes encompassed the prevalence of the FE phenotype and its impact on postoperative complications. A total of 682 patients were screened from June 2014 to October 2015. 93 patients with COPD were included, 21 (23%) were FE. Postoperative tracheobronchitis, atelectasis pneumonia or respiratory failure (isolated or associated) occurred in 47%, 48%, 26%, and 38% of patients, respectively. Non-invasive and invasive mechanical ventilation were necessary in 4 (4%) and 22 (23%) patients. Purulent tracheobronchitis, pneumonia and hypercapnia (this last requiring noninvasive mechanical ventilation) were more frequent in FE (p = 0.043, 0.042, 0.015); however the number of patients wth at least one respiratory complication was not different (76% vs. 52%, p = 0.056). In all patients, multivariate logistic regression identified two independent factors of postoperative respiratory complications: male sex (OR 10.6 [95% CI 1.97-57.6], p = 0.006) and the FE phenotype (OR 6.33 [1.04-38.39], p = 0.045). Occurrence of postoperative complications in patients with COPD is high. FE phenotype is an independent risk factor.

Treatment of exacerbations as a predictor of subsequent outcomes in patients with COPD.

RATIONALE: Exacerbations of COPD are managed differently, but whether treatment of one exacerbation predicts the likelihood of subsequent events is unknown. OBJECTIVE: We examined whether the treatment given for exacerbations predicted subsequent outcomes. METHODS: This was a post-hoc analysis of 17,135 patients with COPD from TIOtropium Safety and Performance In Respimat® (TIOSPIR®). Patients treated with tiotropium with one or more moderate to severe exacerbations on study were analyzed using descriptive statistics, logistic and Cox regression analysis, and Kaplan-Meier plots. RESULTS: Of 8,061 patients with moderate to severe exacerbation(s), demographics were similar across patients with exacerbations treated with antibiotics and/or steroids or hospitalization. Exacerbations treated with systemic corticosteroids alone or in combination with antibiotics had the highest risk of subsequent exacerbation (HR: 1.21, P=0.0004 and HR: 1.33, P<0.0001, respectively), and a greater risk of having a hospitalized (severe) exacerbation (HR: 1.59 and 1.63, P<0.0001, respectively) or death (HR: 1.50, P=0.0059 and HR: 1.47, P=0.0002, respectively) compared with exacerbations treated with antibiotics alone. Initial hospitalization led to the highest risk of subsequent hospitalization (all-cause or COPD related [severe exacerbation], HR: 3.35 and 4.31, P<0.0001, respectively) or death (all-cause or COPD related, HR: 3.53 and 5.54, P<0.0001, respectively) versus antibiotics alone. CONCLUSION: These data indicate that the way exacerbations are treated initially is a useful guide to the patient's subsequent clinical course. Factors that clinicians consider when making treatment choices require further clarification.

Determinants of exacerbation risk in patients with COPD in the TIOSPIR study.

BACKGROUND: Exacerbation history is used to grade the risk of COPD exacerbation, but its reliability and relationship to other risk factors and prior therapy is unclear. To examine these interrelationships, we conducted a post hoc analysis of patients in the TIOSPIR trial with ≥2 years' follow-up or who died on treatment. PATIENTS AND METHODS: Patients were grouped by their annual exacerbation rate on treatment into nonexacerbators, infrequent, and frequent exacerbators (annual exacerbation rates 0, ≤1, and >1, respectively), and baseline characteristics discriminating among the groups were determined. We used univariate and multivariate analyses to explore the effect of baseline characteristics on risk of exacerbation, hospitalization (severe exacerbation), and death (all causes). RESULTS: Of 13,591 patients, 6,559 (48.3%) were nonexacerbators, 4,568 (33.6%) were infrequent exacerbators, and 2,464 (18.1%) were frequent exacerbators; 45% of patients without exacerbations in the previous year exacerbated on treatment. Multivariate analysis identified baseline pulmonary maintenance medication as a predictive factor of increased exacerbation risk, with inhaled corticosteroid treatment associated with increased exacerbation risk irrespective of exacerbation history. CONCLUSION: Our data confirm established risk factors for exacerbation, but highlight the limitations of exacerbation history when categorizing patients and the importance of prior treatment when identifying exacerbation risk.

Safety and tolerability of once-daily tiotropium Respimat(®) as add-on to at least inhaled corticosteroids in adult patients with symptomatic asthma: A pooled safety analysis.

BACKGROUND: Tiotropium, a long-acting anticholinergic bronchodilator, has demonstrated efficacy and safety as add-on therapy to inhaled corticosteroids (ICS), with or without other maintenance therapies, in patients with symptomatic asthma. OBJECTIVE: To evaluate safety and tolerability of tiotropium delivered via the Respimat(®) device, compared with placebo, each as add-on to at least ICS therapy, in a pooled sample of adults with symptomatic asthma at different treatment steps. METHODS: Data were pooled from seven Phase II and III, randomised, double-blind, parallel-group trials of 12-52 weeks' treatment duration, which investigated once-daily tiotropium Respimat(®) (5 µg, 2.5 µg) versus placebo as add-on to different background maintenance therapy including at least ICS. Adverse events (AEs) including serious AEs were assessed throughout treatment + 30 days after the last dose of trial medication. RESULTS: Of 3474 patients analysed, 2157 received tiotropium. The percentage of patients with AEs was comparable between treatment groups: tiotropium 5 µg, 60.8%; placebo 5 µg pool, 62.5%; tiotropium 2.5 µg, 57.1%; placebo 2.5 µg pool, 55.1%. Consistent with the disease profile, the most frequent AEs overall were asthma, decreased peak expiratory flow rate (both less frequent with tiotropium) and nasopharyngitis. Overall incidence of dry mouth, commonly associated with use of anticholinergics, was low: tiotropium 5 µg, 1.0%; placebo 5 µg pool, 0.5%; tiotropium 2.5 µg, 0.4%; placebo 2.5 µg pool, 0.5%. The percentage of cardiac disorder AEs was comparable between tiotropium and placebo: tiotropium 5 µg, 1.4%; placebo 5 µg pool, 1.4%; tiotropium 2.5 µg, 1.4%; placebo 2.5 µg pool, 1.1%. The proportions of patients with serious AEs were balanced across groups: tiotropium 5 µg, 4.0%; placebo 5 µg pool, 4.9%; tiotropium 2.5 µg, 2.0%; placebo 2.5 µg pool, 3.3%. CONCLUSION: Tiotropium Respimat(®) demonstrated safety and tolerability comparable with those of placebo, as add-on to at least ICS therapy, at different treatment steps in adults with symptomatic asthma.

CFTR and/or pancreatitis susceptibility genes mutations as risk factors of pancreatitis in cystic fibrosis patients?

BACKGROUND/OBJECTIVES: Currently, factors that promote the occurrence of pancreatitis episodes in patients affected with cystic fibrosis (CF) and pancreatic sufficiency (PS) are largely unknown. METHODS: Six genes involved in pancreatitis or in ion transport into the pancreatic duct were investigated by next generation sequencing in 59 adult CF-PS patients with two identified CF mutations. Data on predisposing environmental factors were also recorded. RESULTS: 19 experienced at least one episode of acute pancreatitis (AP) (AP+) and 40 patients did not (AP-). No influence of environmental factor was evidenced. No specific CFTR genotype was found predictive of pancreatitis. Patients sharing the same CFTR genotype may or may not experience AP episodes. Frequent and rare missense variants were found in 78.9% patients in group AP+ and 67.5% in group AP- but a few of them were pathogenic. CONCLUSIONS: AP or recurrent AP (RAP) is a frequent complication in our series of adult CF-PS patients. The majority of mild CFTR mutations found in group AP+ were located in the first transmembrane region. No clear other genetic factor could be found predictive of AP/RAP. Further experiments in large homogenous cohorts of CF-PS patients, including whole genome sequencing, may identify genetic predisposing factors to pancreatitis.

Differences in outcomes between GOLD groups in patients with COPD in the TIOSPIR(®) trial.

BACKGROUND: The aim of this study was to evaluate whether Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification could predict mortality risk factors and whether baseline treatment intensity would relate to mortality within each group, using data from TIOSPIR(®), the largest randomized clinical trial in COPD performed to date. METHODS: A total of 17,135 patients from TIOSPIR(®) were pooled and grouped by GOLD grading (A-D) according to baseline Medical Research Council breathlessness score, exacerbation history, and spirometry. All-cause mortality and adjudicated cardiovascular (CV) and respiratory mortality were assessed. RESULTS: Of the 16,326 patients classified, 1,248 died on treatment. Group B patients received proportionally more CV treatment at baseline. CV mortality risk, but not all-cause mortality risk, was significantly higher in Group B than Group C patients (CV mortality - hazard ratio [HR] =1.74, P=0.004; all-cause mortality - HR =1.18, P=0.11). Group D patients had a higher incidence of all-cause mortality than Group B patients (10.9% vs 6.6%). Similar trends were observed regardless of respiratory or CV medication at baseline. In contrast, respiratory deaths increased consistently from Groups A-D (0.3%, 0.8%, 1.6%, and 4.2% of patients, respectively). CONCLUSION: The data obtained from the TIOSPIR(®) trial, supporting earlier studies, suggest that proportionally more CV medication and CV deaths occur in GOLD Group B COPD patients, although deaths attributed to respiratory causes are more prevalent in Groups C and D.

Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat® in Asthma Using Standardized Sample-Contamination Avoidance.

BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat® 5 µg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacokinetic sample contamination resulting from improper sampling procedure, sample handling, or device handling during priming and subsequent inhalation procedure. METHODS: A Phase II, randomized, double-blind, two-way crossover study (NCT01696071) comparing two daily dosing regimens of tiotropium for 4 weeks, once-daily 5 µg (evening dosing) or twice-daily 2.5 µg (morning and evening dosing), as add-on to maintenance therapy with ICS (400-800 µg budesonide or equivalent) as controller medication. There was no washout between treatment periods. RESULTS: An increase in the area under the curve of the 24-hour forced expiratory volume in 1 second profile from study baseline was observed following once-daily tiotropium 5 µg (217 mL) and twice-daily 2.5 µg (219 mL), with no difference between the two regimens (-2 mL [95% confidence interval: -38, 34]). In a subset of the study population, total tiotropium exposure, expressed as area under the plasma concentration versus time curve over 24 hours, was comparable between dosing regimens. Unexpected tiotropium plasma levels were observed in two patients, possibly because of contamination. CONCLUSIONS: The observed bronchodilator efficacy over 24 hours was similar with once-daily tiotropium 5 µg and twice-daily 2.5 µg as add-on to ICS therapy, supporting the suitability of once-daily dosing to provide sustained improvements in lung function in adults with symptomatic asthma.

DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

BACKGROUND AND AIMS: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) patients is associated with worse long-term pulmonary disease and shorter survival, and chronic Pa infection (CPA) is associated with reduced lung function, faster rate of lung decline, increased rates of exacerbations and shorter survival. By using exome sequencing and extreme phenotype design, it was recently shown that isoforms of dynactin 4 (DCTN4) may influence Pa infection in CF, leading to worse respiratory disease. The purpose of this study was to investigate the role of DCTN4 missense variants on Pa infection incidence, age at first Pa infection and chronic Pa infection incidence in a cohort of adult CF patients from a single centre. METHODS: Polymerase chain reaction and direct sequencing were used to screen DNA samples for DCTN4 variants. RESULTS: A total of 121 adult CF patients from the Cochin Hospital CF centre have been included, all of them carrying two CFTR defects: 103 developed at least 1 pulmonary infection with Pa, and 68 patients of them had CPA. DCTN4 variants were identified in 24% (29/121) CF patients with Pa infection and in only 17% (3/18) CF patients with no Pa infection. Of the patients with CPA, 29% (20/68) had DCTN4 missense variants vs 23% (8/35) in patients without CPA. Interestingly, p.Tyr263Cys tend to be more frequently observed in CF patients with CPA than in patients without CPA (4/68 vs 0/35), and DCTN4 missense variants tend to be more frequent in male CF patients with CPA bearing two class II mutations than in male CF patients without CPA bearing two class II mutations (P = 0.06). CONCLUSIONS: Our observations reinforce that DCTN4 missense variants, especially p.Tyr263Cys, may be involved in the pathogenesis of CPA in male CF.

Renin-associated hypertension after bronchial artery embolization in cystic fibrosis.

Bronchial artery embolization is the recommended therapy for massive hemoptysis in patients with cystic fibrosis (CF). We report on two cases of multiple renal infarcts and renin-associated hypertension and hypokalemia occurring in CF adults after bronchial artery embolizations. These complications were presumably related to crossing of small calibrated microspheres through arteriovenous anastomoses. Although hypokalemia resolved rapidly, hypertension persisted at least 6 months and its control required multiple antihypertensive agents. Physicians should be aware of this potentially severe, but previously unreported, complication of bronchial artery embolization.

Safety and efficacy of tiotropium in patients switching from HandiHaler to Respimat in the TIOSPIR trial.

OBJECTIVES: This post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (≥ 2 months) use of tiotropium HandiHaler 18 µg (HH18) prior to study entry, to evaluate whether there was a difference in risk for patients who switched from HH18 to tiotropium Respimat 2.5 µg (R2.5) or 5 g (R5). SETTING: TIOSPIR (n=17,135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial. PARTICIPANTS: Patients from TIOSPIR with chronic obstructive pulmonary disease (COPD) and postbronchodilator ratio of forced expiratory volume in 1 s to forced vital capacity ≤ 0.70, receiving HH18 before study entry, were analysed (n=2784). INTERVENTIONS: Patients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2-3 years. PRIMARY OUTCOMES: time to death (safety) and time to first COPD exacerbation (efficacy). SECONDARY OUTCOMES: number of exacerbations and time to first major adverse cardiovascular event (MACE). RESULTS: Baseline characteristics were similar in all groups. Respimat had a similar mortality risk versus HH18 (vital status follow-up, HR; 95% CI R2.5: 0.87; 0.64 to 1.17; R5: 0.79; 0.58 to 1.07) with no significant differences in the risk and rates of exacerbations and severe exacerbations across treatment groups. Risk of MACE and fatal MACE was similar for Respimat versus HH18 (HR; 95% CI MACE R2.5: 0.73; 0.47 to 1.15; R5: 0.69; 0.44 to 1.08; fatal MACE R2.5: 0.57; 0.27 to 1.19; R5: 0.67; 0.33 to 1.34). Overall risk of a fatal event (on treatment) was lower for R5 versus HH18 (HR; 95% CI R2.5: 0.78; 0.55 to 1.09; R5: 0.62; 0.43 to 0.89). CONCLUSIONS: This analysis indicates that it is safe to switch patients from tiotropium HandiHaler to tiotropium Respimat, and that the efficacy is maintained over the switch. TRIAL REGISTRATION NUMBER: NCT01126437; Post-results.

Safety and efficacy of tiotropium Respimat versus HandiHaler in patients naive to treatment with inhaled anticholinergics: a post hoc analysis of the TIOSPIR trial.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. AIMS: The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 µg had different safety and efficacy outcomes than patients treated with tiotropium HandiHaler 18 µg. METHODS: A post hoc analysis of patients who were not receiving anticholinergics before TIOSPIR (N=6,966/17,135) was conducted. Primary end points were risk of death from any cause and risk of COPD exacerbation. Secondary outcomes included severe exacerbation and major adverse cardiovascular events (MACE). Additional analysis of exacerbations was carried out in anticholinergic-naive patients with moderate (GOLD II) disease. RESULTS: Anticholinergic-naive patients had less severe disease than the total TIOSPIR population. Discontinuations because of anticholinergic side effects were infrequent (0.9% overall). Similar to the primary study, patients in the tiotropium Respimat groups had no difference in the risk of death or risk of any or severe exacerbation than patients treated with tiotropium HandiHaler. Risk of MACE was similar across the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. CONCLUSIONS: Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy.

The Tiotropium Safety and Performance in Respimat® (TIOSPIR®) Trial: Spirometry Outcomes.

BACKGROUND: Tiotropium Safety and Performance in Respimat® (TIOSPIR®) compared the safety and efficacy of tiotropium Respimat® and tiotropium HandiHaler® in patients with chronic obstructive pulmonary disease (COPD). A prespecified spirometry substudy compared the lung function efficacy between treatment groups. METHODS: TIOSPIR® was a large-scale, long-term (2.3-year), event-driven, randomized, double-blind, parallel-group trial of 17,135 patients with COPD. In the spirometry substudy, trough forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured at baseline and every 24 weeks for the duration of the trial. RESULTS: The substudy included 1370 patients who received once-daily tiotropium Respimat® 5 µg (n = 461), 2.5 µg (n = 464), or tiotropium HandiHaler® 18 µg (n = 445). Adjusted mean trough FEV1 (average 24-120 weeks) was 1.285, 1.258, and 1.295 L in the Respimat® 5 µg, 2.5 µg, and HandiHaler® 18 µg groups (difference versus HandiHaler® [95 % CI]: -10 [-38, 18] mL for Respimat® 5 µg and, -37 [-65, -9] mL for Respimat® 2.5 µg); achieving noninferiority to tiotropium HandiHaler® 18 µg for tiotropium Respimat® 5 but not for 2.5 µg (prespecified analysis). Adjusted mean trough FVC was 2.590, 2.544, and 2.593 L in the Respimat® 5 µg, 2.5 µg, and HandiHaler® 18 µg groups. The rates of FEV1 decline over 24 to 120 weeks were similar for the three treatment arms (26, 40, and 34 mL/year for the tiotropium Respimat® 5-µg, 2.5-µg, and HandiHaler® 18-µg groups). The rate of FEV1 decline in GOLD I + II patients was greater than in GOLD III + IV patients (46 vs. 23 mL/year); as well as in current versus ex-smokers, in patients receiving combination therapies at baseline versus not, and in those experiencing an exacerbation during the study versus not. CONCLUSIONS: The TIOSPIR® spirometry substudy showed that tiotropium Respimat® 5 µg was noninferior to tiotropium HandiHaler® 18 µg for trough FEV1, but Respimat® 2.5 µg was not. Tiotropium Respimat® 5 µg provides similar bronchodilator efficacy to tiotropium HandiHaler® 18 µg with comparable rates of FEV1 decline. The rate of FEV1 decline varied based on disease severity, with a steeper rate of decline observed in patients with moderate airway obstruction. TRIAL REGISTRATION: NCT01126437.

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers and patient advocates believe will have the greatest impact on patient-centred outcomes.

An official American Thoracic Society/European Respiratory Society statement: research questions in COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this official American Thoracic Society (ATS)/European Respiratory Society (ERS) research statement is to describe evidence related to diagnosis, assessment and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarised, and then salient knowledge gaps were identified. Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. Great strides have been made in the diagnosis, assessment and management of COPD, as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS research statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centred outcomes.

An Official American Thoracic Society/European Respiratory Society Statement: Research questions in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity, mortality, and resource use worldwide. The goal of this Official American Thoracic Society (ATS)/European Respiratory Society (ERS) Research Statement is to describe evidence related to diagnosis, assessment, and management; identify gaps in knowledge; and make recommendations for future research. It is not intended to provide clinical practice recommendations on COPD diagnosis and management. METHODS: Clinicians, researchers, and patient advocates with expertise in COPD were invited to participate. A literature search of Medline was performed, and studies deemed relevant were selected. The search was not a systematic review of the evidence. Existing evidence was appraised and summarized, and then salient knowledge gaps were identified. RESULTS: Recommendations for research that addresses important gaps in the evidence in all areas of COPD were formulated via discussion and consensus. CONCLUSIONS: Great strides have been made in the diagnosis, assessment, and management of COPD as well as understanding its pathogenesis. Despite this, many important questions remain unanswered. This ATS/ERS Research Statement highlights the types of research that leading clinicians, researchers, and patient advocates believe will have the greatest impact on patient-centered outcomes.