Educational opportunities for postgraduate medical trainees during the COVID-19 pandemic: deriving value from old, new and emerging ways of learning.

The COVID-19 pandemic has had a significant impact on postgraduate medical training across all specialties. Although some traditional learning opportunities have been curtailed, there have been numerous examples of highly valuable educational experiences that have arisen during this time. Here, from a trainee perspective, we consider the educational merits of the re-emergence of 'firm-based' teams, new online learning opportunities, use of digital technologies and the rise of telephone clinics and new COVID-19 clinical services. As health services continue to recover from surges in COVID-19 cases, it is important to reflect on and recognise the value of these educational experiences so that helpful elements can be retained and embedded into training programmes for the benefit of both trainees and patients.

Targeted Retreatment of Incompletely Recovered Chronic Obstructive Pulmonary Disease Exacerbations with Ciprofloxacin. A Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase III Clinical Trial.

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are prone to nonrecovery, but there are no data about the effectiveness of retreatment for these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event.Objectives: To assess whether incompletely recovered COPD exacerbations benefit from additional treatment with ciprofloxacin, at Day 14.Methods: In a multicenter, randomized double-blind placebo-controlled trial, we studied retreatment with oral ciprofloxacin 500 mg or matched placebo twice daily for 7 days in patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV COPD and persistent symptoms and/or serum C-reactive protein ≥8 mg/L initiated 14 (±3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period.Measurements and Main Results: Among 826 patients screened at four centers, 144 eligible participants with incomplete recovery were randomized to receive ciprofloxacin (n = 72) or placebo (n = 72). Within 90 days of randomization, 57% of the patients in the ciprofloxacin group and 53% in the placebo group experienced one or more exacerbations. The median time to the next exacerbation was 32.5 days (interquartile range 13-50) in the placebo arm and 34 days (interquartile range 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio, 1.07; 95% confidence interval, 0.68-1.68; P = 0.76). No significant differences were seen in quality-of-life scores or lung function between the treatment groups.Conclusions: In patients with persistent symptoms and/or raised C-reactive protein 14 days after a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared with placebo. This suggests that nonrecovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with antiinflammatory therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02300220).

Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have increased susceptibility to respiratory tract infection, which contributes to disease progression and mortality, but mechanisms of increased susceptibility to infection remain unclear. OBJECTIVES: The aim of this study was to determine whether glucose concentrations were increased in airway samples (nasal lavage fluid, sputum, and bronchoalveolar lavage fluid) from patients with stable COPD and to determine the effects of viral infection on sputum glucose concentrations and how airway glucose concentrations relate to bacterial infection. METHODS: We measured glucose concentrations in airway samples collected from patients with stable COPD and smokers and nonsmokers with normal lung function. Glucose concentrations were measured in patients with experimentally induced COPD exacerbations, and these results were validated in patients with naturally acquired COPD exacerbations. Relationships between sputum glucose concentrations, inflammatory markers, and bacterial load were examined. RESULTS: Sputum glucose concentrations were significantly higher in patients with stable COPD compared with those in control subjects without COPD. In both experimental virus-induced and naturally acquired COPD exacerbations, sputum and nasal lavage fluid glucose concentrations were increased over baseline values. There were significant correlations between sputum glucose concentrations and sputum inflammatory markers, viral load, and bacterial load. Airway samples with higher glucose concentrations supported more Pseudomonas aeruginosa growth in vitro. CONCLUSIONS: Airway glucose concentrations are increased in patients with stable COPD and further increased during COPD exacerbations. Increased airway glucose concentrations might contribute to bacterial infections in both patients with stable and those with exacerbated COPD. This has important implications for the development of nonantibiotic therapeutic strategies for the prevention or treatment of bacterial infection in patients with COPD.

COPD Multidisciplinary Team Meetings in the United Kingdom: Health Care Professionals' Perceptions of Aims and Structure.

Over the last 10 years, community and hospital-based multidisciplinary teams (MDTs) have been set up for the management of patients with chronic obstructive pulmonary disease (COPD) in the UK. Meetings of the MDTs have become a regular occurrence, mostly on healthcare professionals' own initiatives. There are no standardized methods to conduct an MDT meeting, and although cancer MDT meetings are widely implemented, the value and purpose of COPD MDT meetings are less clear. Therefore, the aim of this study was to conduct a cross-sectional descriptive online survey to explore COPD MDT members' perceptions of the purpose and usefulness of MDT meetings, and to identify suggestions or requirements to improve the meetings. In total, we received 68 responses from 10 MDTs; six teams (n = 36 members) were located in London and four (n = 32 members) outside. Analysis of the replies by two independent researchers found that MDT meetings aim to optimise management and improve pathways for respiratory patients by improving communication between providers across settings and disciplines. Education of the MDT members also occurs with the aim of safer practice. Discussed patients are characterised by (multiple) co-morbidities, frequent exacerbations and admissions, social and mental health problems, unclear diagnosis and suboptimal responses to interventions. Members reported participating in a COPD MDT as very useful (74%) or useful (20%). Meetings could be improved by ensuring attendance through requirement in job plans, by clear documentation and sharing of derived plans with a wider audience including general practitioners and patients.

Breath metabolite response to major upper gastrointestinal surgery.

BACKGROUND: Esophagectomy and gastrectomy are associated with profound metabolic changes and significant postoperative morbidity. The aim of this prospective clinical study was to determine whether breath analysis can offer novel insight into the surgical metabolic response and identify biomarkers of postoperative complications, including lung injury. METHODS: Breath samples were collected preoperatively and at 24, 48, 72, 96 and 168 h after esophagectomy (n = 25) and gastrectomy (n = 15). Targeted analysis of four prominent breath metabolites was performed by selected ion flow-tube mass spectrometry. Patients with nonsurgical lung injury (community-acquired pneumonia) were recruited as positive controls. RESULTS: Perioperative starvation and subsequent reintroduction of nutritional input were associated with significant changes in breath acetone levels. Breath acetone levels fell after esophagectomy (P = 0.008) and were significantly lower than in gastrectomy patients at postoperative time points 48 (P < 0.001) and 72 h (P < 0.001). In contrast, concentrations of isoprene increased significantly after esophagectomy (P = 0.014). Pneumonia was the most frequently observed postoperative complication (esophagectomy 36% and gastrectomy 7%). The concentration of hydrogen cyanide was significantly lower in the breath of patients who developed pneumonia, 72 h after surgery (P = 0.008). Exhaled hydrogen cyanide (P = 0.001) and isoprene (P = 0.014) were also reduced in patients with community-acquired pneumonia compared with healthy controls. CONCLUSIONS: Selected ion flow-tube mass spectrometry can be used as a totally noninvasive resource to monitor multiple aspects of metabolic alterations in the postoperative period. Exhaled concentrations of several prominent metabolites are significantly altered after major upper gastrointestinal surgery and in response to pneumonia.

Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease.

RATIONALE: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections. OBJECTIVES: To investigate relationships between rhinovirus infection and bacterial infection and the role of antimicrobial peptides in COPD exacerbations. METHODS: We infected subjects with moderate COPD and smokers and nonsmokers with normal lung function with rhinovirus. Induced sputum was collected before and repeatedly after rhinovirus infection and virus and bacterial loads measured with quantitative polymerase chain reaction and culture. The antimicrobial peptides secretory leukoprotease inhibitor (SLPI), elafin, pentraxin, LL-37, α-defensins and ß-defensin-2, and the protease neutrophil elastase were measured in sputum supernatants. MEASUREMENTS AND MAIN RESULTS: After rhinovirus infection, secondary bacterial infection was detected in 60% of subjects with COPD, 9.5% of smokers, and 10% of nonsmokers (P < 0.001). Sputum virus load peaked on Days 5-9 and bacterial load on Day 15. Sputum neutrophil elastase was significantly increased and SLPI and elafin significantly reduced after rhinovirus infection exclusively in subjects with COPD with secondary bacterial infections, and SLPI and elafin levels correlated inversely with bacterial load. CONCLUSIONS: Rhinovirus infections are frequently followed by secondary bacterial infections in COPD and cleavage of the antimicrobial peptides SLPI and elafin by virus-induced neutrophil elastase may precipitate these secondary bacterial infections. Therapy targeting neutrophil elastase or enhancing innate immunity may be useful novel therapies for prevention of secondary bacterial infections in virus-induced COPD exacerbations.

Breathlessness and skeletal muscle weakness in patients undergoing lung health screening in primary care.

Earlier diagnosis of COPD is a major public health challenge as symptoms may be attributed to the normal consequences of aging. The optimum strategy for identifying patients with COPD remains to be determined. People aged 35 and over (n = 1896) on a GP practice register were randomised to either invitation or an opportunistic lung health check which included spirometry, quadriceps strength and MRC dyspnoea score. Then, 101 participants subsequently completed the General Practice Physical Activity Questionnaire. A total of 335 attended over a 15-week period; 156 were in the invitation group and 179 from the opportunist group. In 25 persons, spirometry was unsatisfactory or contraindicated. Spirometry was normal in 204(65.8%) and restrictive in 36(11.6%). 70(22.6%) had airflow obstruction, corresponding to Global Initiative for Chronic Lung Disease (GOLD) stages I-IV in 18(5.8%), 35(11.3%), 14(4.5%) and 3(1.0%), respectively. The opportunist group were significantly more likely to have airflow obstruction 30.1% vs 14.3% (p = 0.001). Breathlessness was reported commonly (40.5%) and quadriceps strength correlated significantly with MRC dyspnoea score independent of age, sex, pack-years smoked, fat-free mass and FEV(1) percent predicted. This relationship was also present in the subgroup of healthy participants (n = 143). 51.5% of participants screened were classified as "inactive" and this group were weaker and more breathless than those who were more active. Airflow obstruction was more common in those screened opportunistically. Breathlessness and inactivity are common in patients taking part in spirometry screening. Breathlessness is significantly associated with leg strength independent of spirometry and should be amenable to interventions to increase physical activity.

Finding the missing millions - the impact of a locally enhanced service for COPD on current and projected rates of diagnosis: a population-based prevalence study using interrupted time series analysis.

BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD) are not identified until their condition is relatively advanced and there is a considerable gap between the modelled and diagnosed prevalence of the disease. We have previously shown that, in the first year after the introduction of a locally enhanced service (LES) for COPD in 2008, there was a significant step-up in the diagnosed prevalence. AIMS: To investigate whether this initial increase in prevalence was sustained, and the impact of this increase on future projected rates of COPD diagnosis. METHODS: Using data from 2005-2011, we compared the prevalence of diagnosed COPD in the LES Primary Care Trust (LES-PCT) before and after it was introduced. Data were compared with a neighbouring PCT, the London Strategic Health Authority, and England. The true prevalence of COPD was estimated based on data from the Health Survey for England. Trends were extrapolated to estimate the proportion of patients that would be diagnosed in 2017. RESULTS: The introduction of the LES was associated with a significant acceleration in the annual increase in diagnosed COPD (p<0.0001). By 2011 the prevalence was 1.17% in the LES-PCT compared with a predicted value of 0.91% (95% CI 0.86% to 0.95%) based on the pre-LES trend. There was no change in the rate of increase in COPD prevalence for the neighbouring PCT or for London as a whole. The LES-PCT would be expected to diagnose 55.6% of COPD patients by 2017 compared with only 27.3% without the LES, and only 33.3% would be diagnosed in the neighbouring PCT. CONCLUSIONS: These data suggest that, with appropriate incentives, it is possible to achieve a sustained improvement in COPD case-finding in primary care and that such policies need to be implemented systematically.

Chest CT features and functional correlates of COVID-19 at 3 months and 12 months follow-up.

Long-term pulmonary sequelae of Coronavirus 2019 (COVID-19) remain unclear. Thus, we aimed to establish post-COVID-19 temporal changes in chest computed tomography (CT) features of pulmonary fibrosis and to investigate associations with respiratory symptoms and physiological parameters at 3 and 12 months' follow-up. Adult patients who attended our initial COVID-19 follow-up service and developed chest CT features of interstitial lung disease, in addition to cases identified using British Society of Thoracic Imaging codes, were evaluated retrospectively. Clinical data were gathered on respiratory symptoms and physiological parameters at baseline, 3 months, and 12 months. Corresponding chest CT scans were reviewed by two thoracic radiologists. Associations between CT features and functional correlates were estimated using random effects logistic or linear regression adjusted for age, sex and body mass index. In total, 58 patients were assessed. No changes in reticular pattern, honeycombing, traction bronchiectasis/bronchiolectasis index or pulmonary distortion were observed. Subpleural curvilinear lines were associated with lower odds of breathlessness over time. Parenchymal bands were not associated with breathlessness or impaired lung function overall. Based on our results, we conclude that post-COVID-19 chest CT features of irreversible pulmonary fibrosis remain static over time; other features either resolve or remain unchanged. Subpleural curvilinear lines do not correlate with breathlessness. Parenchymal bands are not functionally significant. An awareness of the different potential functional implications of post-COVID-19 chest CT changes is important in the assessment of patients who present with multi-systemic sequelae of COVID-19 infection.

Designing and implementing a COPD discharge care bundle.

National surveys have revealed significant differences in patient outcomes following admission to hospital with acute exacerbation of COPD which are likely to be due to variations in care. We developed a care bundle, comprising a short list of evidence-based practices to be implemented prior to discharge for all patients admitted with this condition, based on a review of national guidelines and other relevant literature, expert opinion and patient consultation. Implementation was then piloted using action research methodologies with patient input. Actively involving staff was vital to ensure that the changes introduced were understood and the process followed. Implementation of a care bundle has the potential to produce a dramatic improvement in compliance with optimum health care practice.

The transition of adolescents with chronic respiratory illness to adult care.

Medical transition aims to safely steer children with chronic illness through adolescence and into adulthood, whilst maintaining optimal management of their underlying medical condition. It is an evolving process with ongoing research and development. Though it has not been proven to prolong life, evidence points to an improved quality of life via greater understanding and management of lifelong illness. The presumption is this will ultimately prevent or delay untimely loss of life and/or complications in those who have been stable throughout childhood. In this article we review the problems associated with adolescence, the current drive towards successful transition and the role of the adult physician in achieving this.

IL-36 receptor agonist and antagonist imbalance drives neutrophilic inflammation in COPD.

Current treatments fail to modify the underlying pathophysiology and disease progression of chronic obstructive pulmonary disease (COPD), necessitating alternative therapies. Here, we show that COPD subjects have increased IL-36γ and decreased IL-36 receptor antagonist (IL-36Ra) in bronchoalveolar and nasal fluid compared with control subjects. IL-36γ is derived from small airway epithelial cells (SAEC) and is further induced by a viral mimetic, whereas IL-36Ra is derived from macrophages. IL-36γ stimulates release of the neutrophil chemoattractants CXCL1 and CXCL8, as well as elastolytic matrix metalloproteinases (MMPs) from small airway fibroblasts (SAF). Proteases released from COPD neutrophils cleave and activate IL-36γ, thereby perpetuating IL-36 inflammation. Transfer of culture media from SAEC to SAF stimulated release of CXCL1, which was inhibited by exogenous IL-36Ra. The use of a therapeutic antibody that inhibits binding to the IL-36R attenuated IL-36γ-driven inflammation and cellular crosstalk. We have demonstrated a mechanism for the amplification and propagation of neutrophilic inflammation in COPD and have shown that blocking this cytokine family via a IL-36R neutralizing antibody could be a promising therapeutic strategy in the treatment of COPD.

Recovering from COVID-19: lessons learnt from an intensive secondary care follow-up service.

In response to the first COVID-19 surge in 2020, secondary care outpatient services were rapidly reconfigured to provide specialist review for disease sequelae. At our institution, comprising hospitals across three sites in London, we initially implemented a COVID-19 follow-up pathway that was in line with expert opinion at the time but more intensive than initial clinical guidelines suggested. We retrospectively evaluated the resource requirements for this service, which supported 526 patients from April 2020 to October 2020. At the 6-week review, 193/403 (47.9%) patients reported persistent breathlessness, 46/336 (13.7%) desaturated on exercise testing, 167/403 (41.4%) were discharged from COVID-19-related secondary care services and 190/403 (47.1%) needed 12-week follow-up. At the 12-week review, 113/309 (36.6%) patients reported persistent breathlessness, 30/266 (11.3%) desaturated on exercise testing and 150/309 (48.5%) were discharged from COVID-19-related secondary care services. Referrals were generated to multiple medical specialties, particularly respiratory subspecialties. Our analysis allowed us to justify rationalising and streamlining provisions for subsequent COVID-19 waves while reassured that opportunities for early intervention were not being missed.

Qualitative Study of Practices and Challenges of Stepping Down Asthma Medication in Primary Care Across the UK.

BACKGROUND: Guidelines recommend that asthma treatment should be stepped down to the minimally effective dose that achieves symptom control to prevent medication side effects and reduce unnecessary costs. Little is known about the practice of stepping down and the challenges in primary care, where most asthma patients are managed. OBJECTIVE: To explore views, experiences, barriers and ideas, of doctors, nurses and pharmacists working in primary care, related to step down of asthma medication. METHODS: Primary care practitioners from across the UK participated in a survey and/or semi-structured interview. Questions explored four main areas: how asthma medication is reviewed, views on asthma guidelines, perceived barriers faced by healthcare workers and facilitators of stepping down. Qualitative content analysis enabled data coding of interview transcripts to identify major themes. RESULTS: A total of 274 participants responded to the survey, 29 participated in an interview (12 doctors, 9 nurses, and 8 pharmacists), working in GP practices from across the UK. Nearly half of the survey participants infrequently step down asthma medication (doctors=42.7%, nurses=46.3%). Four major themes related to barriers to stepping down were (i) lack of awareness of the need to step down, (ii) inertia to step down, driven by low confidence in ability, fear of consequences, and concern for who is responsible for stepping down, (iii) self-efficacy of ability to step down, influenced by lack of clear, applied guidance and limited training, and (iv) feasibility of step down, driven by a lack of systematic acceptance of stepping down and time. Strategies proposed to reduce overtreatment included education and training, improved gathering of evidence and guidance, and integrating step down into routine asthma care. CONCLUSION: Failure to implement this guideline recommendation into everyday asthma management is influenced by several contributing factors. Future directions should include addressing evidence gaps, implementing clear and practical guidance, integration of step-down assessment into the asthma review, and education of professionals and patients.

Respiratory specialists working in different ways: Development of a GP hotline and respiratory support service during the COVID-19 pandemic.

Integration of primary and secondary care for the management of respiratory disease is a long-held ambition. Here, we describe how respiratory specialists at a large NHS trust, working with primary care clinicians in the area, set up a GP hotline and respiratory support service in response to the COVID-19 pandemic, with the aim of enhancing delivery of care to patients in this unprecedented time. Working across traditional organisational boundaries in this way confers benefits to patients and clinicians, illustrating the value of new, integrated models of care.

Management of Fracture Risk in Patients with Chronic Obstructive Pulmonary Disease (COPD): Building a UK Consensus Through Healthcare Professional and Patient Engagement.

Introduction: Osteoporosis and bone fractures are common in chronic obstructive pulmonary disease (COPD) and contribute significantly to morbidity and mortality. Current national guidance on COPD management recommends addressing bone health in patients, however, does not detail how. This consensus outlines key elements of a structured approach to managing bone health and fracture risk in patients with COPD. Methods: A systematic approach incorporating multifaceted methodologies included detailed patient and healthcare professional (HCP) surveys followed by a roundtable meeting to reach a consensus on what a pathway would look like. Results: The surveys revealed that fracture risk was not always assessed despite being recognised as an important aspect of COPD management by HCPs. The majority of the patients also stated they would be receptive to discussing treatment options if found to be at risk of osteoporotic fractures. Limited time and resource allocation were identified as barriers to addressing bone health during consultations. The consensus from the roundtable meeting was that a proactive systematic approach to assessing bone health should be adopted. This should involve using fracture risk assessment tools to identify individuals at risk, investigating secondary causes of osteoporosis if a diagnosis is made and reinforcing non-pharmacological and preventative measures such as smoking cessation, keeping active and pharmacological management of osteoporosis and medicines management of corticosteroid use. Practically, prioritising patients with important additional risk factors, such as previous fragility fractures, older age and long-term oral corticosteroid use for an assessment, was felt required. Conclusion: There is a need for integrating fracture risk assessment into the COPD pathway. Developing a systematic and holistic approach to addressing bone health is key to achieving this. In tandem, opportunities to disseminate the information and educational resources are also required.

Technology and its role in respiratory care.

INTRODUCTION: Telemonitoring, telemedicine, clinical and medical informatics or telecare, are terms used to describe the use of technology along with local clinical protocols to monitor remotely a patient's medical condition in their own home. In respiratory medicine, where large numbers of people have long term conditions such as asthma and chronic obstructive pulmonary disease (COPD), the role of such monitoring technology in the management of patients is of great interest. AIM: This review seeks to explore what evidence exists to support the deployment of technology to improve the care of people with respiratory conditions. METHOD: Narrative review. RESULT: A wide variety of technologies have been involved in asthma and COPD care, from management systems to self monitoring devices. Many studies report that staff and patients 'liked' the technology. The service, care and financial benefits to both patients and the health care system were less obvious. Many studies suffered from poor methodology and lacked clear endpoints. CONCLUSION: There is an enormous potential for telemonitoring to assist in the provision of better care for those with long term lung diseases. However, evidence of benefit is unclear and there remains a need for robust studies and answers to clear research questions for specific patient populations before such technologies can be recommended for widespread implementation.

Validity of the diagnosis of pneumonia in hospitalised patients with COPD.

RATIONALE: Exacerbations of chronic obstructive pulmonary disease (COPD) and pneumonia are two of the most common reasons for acute hospital admissions. Acute exacerbations and pneumonia present with similar symptoms in COPD patients, representing a diagnostic challenge with a significant impact on patient outcomes. The objectives of this study were to compare the prevalence of radiographic consolidation with the discharge diagnoses of hospitalised COPD patients. METHODS: COPD patients admitted to three UK hospitals over a 3-year period were identified. Participants were included if they were admitted with an acute respiratory illness, COPD was confirmed by spirometry and a chest radiograph was performed within 24 h of admission. Pneumonia was defined as consolidation on chest radiograph reviewed by two independent observers. RESULTS: There were 941 admissions in 621 patients included in the final analysis. In 235 admissions, consolidation was present on chest radiography and there were 706 admissions without consolidation. Of the 235 admissions with consolidation, only 42.9% had a discharge diagnosis of pneumonia; 90.7% of patients without consolidation had a discharge diagnosis of COPD exacerbation. The presence of consolidation was associated with increased rate of high-dependency care admission, increased mortality and prolonged length of stay. Inhaled corticosteroid use was associated with recurrent pneumonia. CONCLUSIONS: Pneumonia is underdiagnosed in patients with COPD. Radiographic consolidation is associated with worse outcomes and prolonged length of stay. Incorrect diagnosis could result in inappropriate use of inhaled corticosteroids. Future guidelines should specifically address the diagnosis and management of pneumonia in COPD.

Inflammation and infections in unreported chronic obstructive pulmonary disease exacerbations.

Purpose: COPD patients often do not report acute exacerbations to healthcare providers - unreported exacerbations. It is not known whether variances in symptoms, airway obstruction, aetiology and inflammatory responses account for differences in reporting of COPD exacerbations. The aims of the study were to compare symptoms, lung function changes, aetiology and inflammatory markers between exacerbations that were reported to healthcare providers or treated, with those that were unreported and untreated. Patients and methods: We recruited a cohort of COPD patients and collected clinical data and blood and airway samples when stable and during acute exacerbations. Virological and bacterial analyses were carried out and inflammatory markers measured. Results: We found no differences in symptoms, lung function, incidence of infection and inflammatory markers between reported and unreported exacerbations. Subjects who reported all exacerbations had higher BODE scores, lower FEV1 and more exacerbations compared with those who did not. Conclusion: The failure to report exacerbations is not related to the severity, aetiology or inflammatory profile of the exacerbation. Patients with less severe COPD and less frequent exacerbations are less likely to report exacerbations. The decision to report an exacerbation is not an objective marker of exacerbation severity and therefore studies that do not count unreported exacerbations will underestimate the frequency of clinically significant exacerbations. A better understanding of the factors that determine non-reporting of exacerbations is required to improve exacerbation reporting. Trial registration: ClinicalTrials.gov Identifier: NCT01376830. Registered June 17, 2011.