Impact of Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma on Symptoms, Quality of Life, Healthcare Use, and Work Productivity.

Rationale: A significant proportion of individuals with chronic obstructive pulmonary disease (COPD) and asthma remain undiagnosed. Objectives: The objective of this study was to evaluate symptoms, quality of life, healthcare use, and work productivity in subjects with undiagnosed COPD or asthma compared with those previously diagnosed, as well as healthy control subjects. Methods: This multicenter population-based case-finding study randomly recruited adults with respiratory symptoms who had no previous history of diagnosed lung disease from 17 Canadian centers using random digit dialing. Participants who exceeded symptom thresholds on the Asthma Screening Questionnaire or the COPD Diagnostic Questionnaire underwent pre- and post-bronchodilator spirometry to determine if they met diagnostic criteria for COPD or asthma. Two control groups, a healthy group without respiratory symptoms and a symptomatic group with previously diagnosed COPD or asthma, were similarly recruited. Measurements and Main Results: A total of 26,905 symptomatic individuals were interviewed, and 4,272 subjects were eligible. Of these, 2,857 completed pre- and post-bronchodilator spirometry, and 595 (21%) met diagnostic criteria for COPD or asthma. Individuals with undiagnosed COPD or asthma reported greater impact of symptoms on health status and daily activities, worse disease-specific and general quality of life, greater healthcare use, and poorer work productivity than healthy control subjects. Individuals with undiagnosed asthma had symptoms, quality of life, and healthcare use burden similar to those of individuals with previously diagnosed asthma, whereas subjects with undiagnosed COPD were less disabled than those with previously diagnosed COPD. Conclusions: Undiagnosed COPD or asthma imposes important, unmeasured burdens on the healthcare system and is associated with poor health status and negative effects on work productivity.

Patient and physician factors associated with symptomatic undiagnosed asthma or COPD.

BACKGROUND: It remains unclear why some symptomatic individuals with asthma or COPD remain undiagnosed. Here, we compare patient and physician characteristics between symptomatic individuals with obstructive lung disease (OLD) who are undiagnosed and individuals with physician-diagnosed OLD. METHODS: Using random-digit dialling and population-based case finding, we recruited 451 participants with symptomatic undiagnosed OLD and 205 symptomatic control participants with physician-diagnosed OLD. Data on symptoms, quality of life and healthcare utilisation were analysed. We surveyed family physicians of participants in both groups to elucidate differences in physician practices that could contribute to undiagnosed OLD. RESULTS: Participants with undiagnosed OLD had lower mean pre-bronchodilator forced expiratory volume in 1 s percentage predicted compared with those who were diagnosed (75.2% versus 80.8%; OR 0.975, 95% CI 0.963-0.987). They reported greater psychosocial impacts due to symptoms and worse energy and fatigue than those with diagnosed OLD. Undiagnosed OLD was more common in participants whose family physicians were practising for >15 years and in those whose physicians reported that they were likely to prescribe respiratory medications without doing spirometry. Undiagnosed OLD was more common among participants who had never undergone spirometry (OR 10.83, 95% CI 6.18-18.98) or who were never referred to a specialist (OR 5.92, 95% CI 3.58-9.77). Undiagnosed OLD was less common among participants who had required emergency department care (OR 0.44, 95% CI 0.20-0.97). CONCLUSIONS: Individuals with symptomatic undiagnosed OLD have worse pre-bronchodilator lung function and present with greater psychosocial impacts on quality of life compared with their diagnosed counterparts. They were less likely to have received appropriate investigations and specialist referral for their respiratory symptoms.

Disease burden in individuals with symptomatic undiagnosed asthma or COPD.

BACKGROUND: The actual burden of COPD and asthma may be much higher than appreciated, since a large proportion of individuals are not diagnosed. Our study objective was to compare health care utilization, burden of symptoms and quality of life in subjects with self-reported respiratory symptoms who were subsequently found to have undiagnosed airflow obstruction compared to those having no airflow obstruction. METHODS: This cross-sectional case-finding study used data from the Undiagnosed COPD and Asthma Population (UCAP) study. Adult subjects with respiratory symptoms who had no history of diagnosed lung disease were recruited in a two-step case-finding process using random digit-dialling of land lines and cell phones located within a 90-min radius of 16 Canadian study sites. Participants were assessed for COPD, asthma or no airflow obstruction using pre- and post-bronchodilator spirometry based on American Thoracic Society diagnostic criteria. RESULTS: 1660 participants were recruited, of these 1615 had adequate spirometry and 331 (20.5%) subjects met spirometry criteria for undiagnosed asthma or COPD. Subjects with undiagnosed asthma or COPD had increased respiratory symptoms as assessed by the COPD Assessment Test (CAT), and higher St. George's Respiratory Questionnaire (SGRQ) scores indicating worse health-related quality of life, compared to subjects with no airflow obstruction. No between-group differences were found in health care utilization or work or school absenteeism. CONCLUSION: Undiagnosed asthma and COPD are common in Canadian adults experiencing breathing problems and are associated with a greater burden of symptoms and poorer health-related quality of life. These results suggest that patients may benefit from early identification and treatment of undiagnosed asthma and COPD.

Derivation and validation of the UCAP-Q case-finding questionnaire to detect undiagnosed asthma and COPD.

BACKGROUND: Many people with asthma and COPD remain undiagnosed. We developed and validated a new case-finding questionnaire to identify symptomatic adults with undiagnosed obstructive lung disease. METHODS: Adults in the community with no prior history of physician-diagnosed lung disease who self-reported respiratory symptoms were contacted via random-digit dialling. Pre- and post-bronchodilator spirometry was used to confirm asthma or COPD. Predictive questions were selected using multinomial logistic regression with backward elimination. Questionnaire performance was assessed using sensitivity, predictive values and area under the receiver operating characteristic curve (AUC). The questionnaire was assessed for test-retest reliability, acceptability and readability. External validation was prospectively conducted in an independent sample and predictive performance re-evaluated. RESULTS: A 13-item Undiagnosed COPD and Asthma Population Questionnaire (UCAP-Q) case-finding questionnaire to predict undiagnosed asthma or COPD was developed. The most appropriate risk cut-off was determined to be 6% for either disease. Applied to the derivation sample (n=1615), the questionnaire yielded a sensitivity of 92% for asthma and 97% for COPD; specificity of 17%; and an AUC of 0.69 (95% CI 0.64-0.74) for asthma and 0.82 (95% CI 0.78-0.86) for COPD. Prospective validation using an independent sample (n=471) showed sensitivities of 93% and 92% for asthma and COPD, respectively; specificity of 19%; with AUCs of 0.70 (95% CI 0.62-0.79) for asthma and 0.81 (95% CI 0.74-0.87) for COPD. AUCs for UCAP-Q were higher compared to AUCs for currently recommended case-finding questionnaires for asthma or COPD. CONCLUSIONS: The UCAP-Q demonstrated high sensitivities and AUCs for identifying undiagnosed asthma or COPD. A web-based calculator allows for easy calculation of risk probabilities for each disease.

Population-based case-finding to identify subjects with undiagnosed asthma or COPD.

BACKGROUND: ∼5-10% of adults may have undiagnosed airflow obstruction. The objective of this study was to develop a population-based case-finding strategy to assess the prevalence of undiagnosed airflow obstruction (asthma or COPD) amongst adults with respiratory symptoms in Canada. METHODS: Adults without a previous history of asthma, COPD or lung disease were recruited using random digit-dialling and asked if they had symptoms of dyspnoea, cough, sputum or wheeze within the past 6 months. Those who answered affirmatively completed the Asthma Screening Questionnaire (ASQ), COPD-Diagnostic Questionnaire (COPD-DQ) and COPD Assessment Test (CAT). Those with an ASQ score of ≥6 or a COPD-DQ score of ≥20 underwent pre- and post-bronchodilator spirometry to diagnose asthma or COPD. RESULTS: 12 117 individuals were contacted at home and assessed for study eligibility. Of the 1260 eligible individuals, 910 (72%) enrolled and underwent spirometry. Ultimately, 184 subjects (20% of those enrolled) had obstructive lung disease (73 asthma and 111 COPD). Individuals found to have undiagnosed asthma or COPD had more severe respiratory symptoms and impaired quality of life compared with those without airflow obstruction. The ASQ, COPD-DQ, and CAT had ROC areas for predicting undiagnosed asthma or COPD of 0.49, 0.64 and 0.56, respectively. Four descriptive variables (age, BMI, sex and pack-years smoked) produced better receiver operating characteristic (ROC) values than the questionnaires (ROC area=0.68). CONCLUSION: 20% of randomly selected individuals who report respiratory symptoms in Canada have undiagnosed airflow obstruction due to asthma or COPD. Questionnaires could exclude subjects at low risk but lack the ability to accurately find subjects with undiagnosed disease.

Performance Characteristics of Spirometry With Negative Bronchodilator Response and Methacholine Challenge Testing and Implications for Asthma Diagnosis.

BACKGROUND: In patients with a history suggestive of asthma, diagnosis is usually confirmed by spirometry with bronchodilator response (BDR) or confirmatory methacholine challenge testing (MCT). RESEARCH QUESTION: We examined the proportion of participants with negative BDR testing who had a positive MCT (and its predictors) result and characteristics of MCT, including effects of controller medication tapering and temporal variability (and predictors of MCT result change), and concordance between MCT and pulmonologist asthma diagnosis. STUDY DESIGN AND METHODS: Adults with self-reported physician-diagnosed asthma were recruited by random-digit dialing across Canada. Subjects performed spirometry with BDR testing and returned for MCT if testing was nondiagnostic for asthma. Subjects on controllers underwent medication tapering with serial MCTs over 3 to 6 weeks. Subjects with a negative MCT (the provocative concentration of methacholine that results in a 20% drop in FEV1 [PC20] > 8 mg/mL) off medications were examined by a pulmonologist and had serial MCTs after 6 and 12 months. RESULTS: Of 500 subjects (50.5 ± 16.6 years old, 68.0% female) with a negative BDR test for asthma, 215 (43.0%) had a positive MCT. Subjects with prebronchodilator airflow limitation were more likely to have a positive MCT (OR, 1.90; 95% CI, 1.17-3.04). MCT converted from negative to positive, with medication tapering in 18 of 94 (19.1%) participants, and spontaneously over time in 25 of 165 (15.2%) participants. Of 231 subjects with negative MCT, 28 (12.1%) subsequently received an asthma diagnosis from a pulmonologist. INTERPRETATION: In subjects with a self-reported physician diagnosis of asthma, absence of bronchodilator reversibility had a negative predictive value of only 57% to exclude asthma. A finding of spirometric airflow limitation significantly increased chances of asthma. MCT results varied with medication taper and over time, and pulmonologists were sometimes prepared to give a clinical diagnosis of asthma despite negative MCT. Correspondingly, in patients for whom a high clinical suspicion of asthma exists, repeat testing appears to be warranted.

Women with COPD.

Health inequalities regarding gender are extremely prevalent, and specifically in conditions such as COPD. No woman should ever be dismissed in regard to their health and underlying medical history. https://bit.ly/2X7Klmd.

Between-Visit Variability in FEV1 as a Diagnostic Test for Asthma in Adults.

RATIONALE: The reliability of using between-visit variation in forced expiratory volume in 1 second (FEV1) to diagnose asthma is understudied, and hence uncertain. OBJECTIVE: To determine whether FEV1 variability measured over recurrent visits is significantly associated with a diagnosis of current asthma. METHODS: Randomly selected adults (N = 964) with a history of physician-diagnosed asthma were studied from 2005 to 2007 and from 2012 to 2016. A diagnosis of current asthma was confirmed in those participants who exhibited bronchial hyperresponsiveness to methacholine and/or acute worsening of asthma symptoms while being weaned off asthma medications. Regression analyses and receiver operating curves were used to evaluate the ability of between-visit FEV1 variability to diagnose asthma. RESULTS: A current diagnosis of asthma was confirmed in 584 of 964 participants (60%). Between-visit absolute variability in FEV1 was significantly greater in those in whom current asthma was confirmed, compared with those in whom current asthma was ruled out (7.3% vs. 4.8%; mean difference between the two groups, 2.5%; 95% confidence interval, 1.7-3.3%). However, a 12% and 200-ml between-visit variation in FEV1, which is the diagnostic threshold recommended by Global Initiative for Asthma, exhibited a sensitivity of only 0.17 and a specificity of 0.94 for confirming current asthma. A between-visit absolute variability in FEV1 ≥ 12% and 200 ml increased the pretest probability of asthma from 60% to a posttest probability of 81%. CONCLUSIONS: A 12% and 200-ml between-visit variation in FEV1, if present, has reasonably good specificity for diagnosing asthma, but has poor sensitivity compared with bronchial challenge testing. Between-visit variability in FEV1 is a relatively unhelpful test to establish a diagnosis of asthma.

Optimizing the Delivery of Inhaled Medication for Respiratory Patients: The Role of Valved Holding Chambers.

Valved holding chambers (VHCs) have been used with pressurized metered-dose inhalers since the early 1980s. They have been shown to increase fine particle delivery to the lungs, decrease oropharyngeal deposition, and reduce side effects such as throat irritation, dysphonia, and oral candidiasis that are common with use of pressurized metered-dose inhalers (pMDIs) alone. VHCs act as aerosol reservoirs, allowing the user to actuate the pMDI device and then inhale the medication in a two-step process that helps users overcome challenges in coordinating pMDI actuation with inhalation. The design of VHC devices can have an impact on performance. Features such as antistatic properties, effective face-to-facemask seal feedback whistles indicating correct inhalation speed, and inhalation indicators all help improve function and performance, and have been demonstrated to improve asthma control, reduce the rate of exacerbations, and improve quality of life. Not all VHCs are the same, and they are not interchangeable. Each pairing of a pMDI device plus VHC should be considered as a unique delivery system.

The evolving role of tiotropium in asthma.

Tiotropium is a long-acting muscarinic antagonist (LAMA) that exerts its bronchodilatory effect by blocking endogenous acetylcholine receptors in the airways. Its safety and efficacy are well established for the treatment of COPD, and it is now being recognized for its role in improving lung function and control in asthma. This review discusses the evolving role of tiotropium delivered by the Respimat® in patients across the range of asthma severities and ages, and provides an overview of safety and efficacy data. Tiotropium is the only LAMA currently approved for the treatment of asthma, and evidence from a large-scale clinical trial program, including several Phase III studies in adults, has demonstrated that tiotropium improves lung function and asthma control, with a safety profile comparable with that of placebo. Clinical trials in adolescent patients (aged 12-17 years) have also shown improvements in lung function and trends toward improved asthma control. Of note, the efficacy and safety profiles are consistent regardless of baseline characteristics and phenotype. Given the large and growing body of evidence, it is likely that as clinical experience with tiotropium increases, this treatment may possibly emerge as the key choice for add-on therapy to inhaled corticosteroids/long-acting ß2-agonists, and in patients who do not tolerate long-acting bronchodilators or other medications, in the future.

Effective deployment of technology-supported management of chronic respiratory conditions: a call for stakeholder engagement.

BACKGROUND: Healthcare systems are under increasing strain, predominantly due to chronic non-communicable diseases. Connected healthcare technologies are becoming ever more capable and their components cheaper. These innovations could facilitate both self-management and more efficient use of healthcare resources for common respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, newer technologies can only facilitate major changes in practice, and cannot accomplish them in isolation. FOCUS OF REVIEW: There are now large numbers of devices and software offerings available. However, the potential of such technologies is not being realised due to limited engagement with the public, clinicians and providers, and a relative paucity of evidence describing elements of best practice in this complex and evolving environment. Indeed, there are clear examples of wasted resources and potential harm. We therefore call on interested parties to work collaboratively to begin to realize the potential benefits and reduce the risks of connected technologies through change in practice. We highlight key areas where such partnership can facilitate the effective and safe use of technology in chronic respiratory care: developing data standards and fostering inter-operability, making collaborative testing facilities available at scale for small to medium enterprises, developing and promoting new adaptive trial designs, developing robust health economic models, agreeing expedited approval pathways, and detailed planning of dissemination to use. CONCLUSION: The increasing capability and availability of connected technologies in respiratory care offers great opportunities and significant risks. A co-ordinated collaborative approach is needed to realize these benefits at scale. Using newer technologies to revolutionize practice relies on widespread engagement and cannot be delivered by a minority of interested specialists. Failure to engage risks a costly and inefficient chapter in respiratory care.

Colds as predictors of the onset and severity of COPD exacerbations.

RATIONALE: Common colds are associated with acute respiratory symptom exacerbations in COPD patients. OBJECTIVE: To determine exacerbation risk and severity in COPD patients with/without coincident self-reported colds. METHODS: Global initiative for chronic Obstructive Lung Disease stage I-IV COPD patients electronically transmitted respiratory symptom diaries to research staff daily between December 2006 and April 2009. Respiratory symptom worsening prompted contact by a study nurse and patient assessment to determine if a cold was present or an exacerbation underway. A composite daily symptom score was derived for each subject from diarized symptom data. The exacerbation/cold/virus relation was examined using a Poisson regression model, the relation of colds to respiratory symptom severity using generalized estimating equation models. RESULTS: Daily diary transmission compliance of >97% enabled detection of all possible exacerbations. Among 262 exacerbations meeting Anthonisen criteria, 218 (83%) had cold-like symptoms present at their inception, but respiratory viruses were detected in only 106 (40%). Within-subject exacerbation risk was 30 times (95% confidence interval [CI]: 20, 47; P<0.001) greater with colds present. Compared to cold- and virus-negative exacerbations (n=57), the mean increase in composite symptom score in those cold and virus positive (n=79) was 0.93 (95% CI: 0.61, 1.25; P<0.001), cold-positive and virus-negative exacerbations (n=100) 0.51 (95% CI: 0.21, 0.81; P<0.001), cold-negative and virus-positive exacerbations (n=26) 0.58 (95% CI: 0.23, 0.94; P<0.001). CONCLUSION: This study emphasizes the importance of colds in COPD exacerbation risk and severity, even in the absence of virus detection. COPD patients should act promptly when cold symptoms appear to facilitate early intervention for exacerbation prevention or management.

Reevaluation of Diagnosis in Adults With Physician-Diagnosed Asthma.

Importance: Although asthma is a chronic disease, the expected rate of spontaneous remissions of adult asthma and the stability of diagnosis are unknown. Objective: To determine whether a diagnosis of current asthma could be ruled out and asthma medications safely stopped in randomly selected adults with physician-diagnosed asthma. Design, Setting, and Participants: A prospective, multicenter cohort study was conducted in 10 Canadian cities from January 2012 to February 2016. Random digit dialing was used to recruit adult participants who reported a history of physician-diagnosed asthma established within the past 5 years. Participants using long-term oral steroids and participants unable to be tested using spirometry were excluded. Information from the diagnosing physician was obtained to determine how the diagnosis of asthma was originally made in the community. Of 1026 potential participants who fulfilled eligibility criteria during telephone screening, 701 (68.3%) agreed to enter into the study. All participants were assessed with home peak flow and symptom monitoring, spirometry, and serial bronchial challenge tests, and those participants using daily asthma medications had their medications gradually tapered off over 4 study visits. Participants in whom a diagnosis of current asthma was ultimately ruled out were followed up clinically with repeated bronchial challenge tests over 1 year. Exposure: Physician-diagnosed asthma established within the past 5 years. Main Outcomes and Measures: The primary outcome was the proportion of participants in whom a diagnosis of current asthma was ruled out, defined as participants who exhibited no evidence of acute worsening of asthma symptoms, reversible airflow obstruction, or bronchial hyperresponsiveness after having all asthma medications tapered off and after a study pulmonologist established an alternative diagnosis. Secondary outcomes included the proportion with asthma ruled out after 12 months and the proportion who underwent an appropriate initial diagnostic workup for asthma in the community. Results: Of 701 participants (mean [SD] age, 51 [16] years; 467 women [67%]), 613 completed the study and could be conclusively evaluated for a diagnosis of current asthma. Current asthma was ruled out in 203 of 613 study participants (33.1%; 95% CI, 29.4%-36.8%). Twelve participants (2.0%) were found to have serious cardiorespiratory conditions that had been previously misdiagnosed as asthma in the community. After an additional 12 months of follow-up, 181 participants (29.5%; 95% CI, 25.9%-33.1%) continued to exhibit no clinical or laboratory evidence of asthma. Participants in whom current asthma was ruled out, compared with those in whom it was confirmed, were less likely to have undergone testing for airflow limitation in the community at the time of initial diagnosis (43.8% vs 55.6%, respectively; absolute difference, 11.8%; 95% CI, 2.1%-21.5%). Conclusions and Relevance: Among adults with physician-diagnosed asthma, a current diagnosis of asthma could not be established in 33.1% who were not using daily asthma medications or had medications weaned. In patients such as these, reassessing the asthma diagnosis may be warranted.

Emerging therapeutic options for the treatment of patients with symptomatic asthma.

OBJECTIVE: Asthma is a chronic inflammatory disorder of the airways with increasing worldwide prevalence. Despite treatment according to guidelines, a considerable proportion of patients with asthma remain symptomatic. Different potential therapeutic options for the treatment of these patients are currently in development and undergoing clinical trials, and it is important to regularly review their status. DATA SOURCES: A search of ClinicalTrials.gov was performed and supported by a PubMed literature search and restricted to the previous 10 years to ensure currency of data. The results were manually filtered to identify relevant articles. STUDY SELECTIONS: Emerging therapies that are currently in phase 2 and 3 development include anti-interleukin agents (benralizumab, reslizumab, dupilumab, brodalumab, lebrikizumab, and mepolizumab), a chemoattractant receptor-homologous molecule expressed on a T-helper type 2 lymphocyte antagonist (OC000459), a phosphodiesterase-4 inhibitor (roflumilast), and long-acting muscarinic antagonists (glycopyrronium bromide, umeclidinium bromide, and tiotropium bromide). RESULTS: The clinical trial program of the long-acting muscarinic antagonist tiotropium is currently the most advanced, with data available from different phase 2 and 3 studies. Results demonstrate that it is an efficacious add-on to at least inhaled corticosteroid maintenance therapy across severities of symptomatic asthma. CONCLUSION: The results of ongoing and future studies will help to determine whether these emerging therapeutic options will help address the unmet need for improvement in asthma management.

Integrating patients into meaningful real-world research.

Research in respiratory, sleep, and critical care medicine has historically been the domain of scientists and clinicians attempting to understand pathophysiological mechanisms and consequences of disease in an effort to develop effective treatments. This traditional approach of placing scientific rigor before the patient's reality is changing. There is growing recognition of the importance of integrating patient perspectives (e.g., preferences, expectations, and expanded definitions of what constitutes "successful" outcomes) into clinical research to achieve meaningful results for a broader group of stakeholders. This evolution is reflected in the growth of patient-centered organizations and patient advocacy groups that seek to meaningfully integrate patients into the process of prioritizing research needs and creating alliances wherein patients and researchers can partner together to accomplish research goals. In tandem, a growing number of real-world trials (i.e., those with broader, more representative patient populations and routine care pathways) now complement findings from traditional randomized controlled trials and offer new opportunities to design studies that better reflect patients' healthcare preferences and experiences. Patients' perspectives are key determinants of treatment adherence and outcomes, as well as the feasibility and likely value of implementing care pathways. The advent of smartphone and push technologies offer new opportunities for the collection of more patient-centered and ecologically valid patient data, thereby adding new dimensions to meaningfully integrate patients into real-world research.

Emerging concepts and therapies for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Although considerable advances have been made in the diagnosis and treatment of COPD, much remains to be done both to alleviate symptoms and reduce mortality associated with this condition. Previously, diagnosis, management, and research all centred on staging based on the forced expiratory flow in 1 second. It is now becoming apparent that this is inadequate to truly capture current disease burden and future deterioration. Fortunately, new approaches to care are constantly being identified. It is now known that symptoms and, in particular, exacerbations represent pivotal events in the patient's life that should trigger optimization of care. Much work is currently underway to identify various phenotypes in COPD because it has become obvious that this is a heterogeneous disease and applying the same management algorithms for all patients is insufficient. Several new medications are at various stages of development, some being approved and on the market, while others are undergoing clinical trials. These allow for more options for individualized care of patients. In addition, new applications of old medications, such as long­term antibiotics, also provide new options for patients struggling with recurrent symptoms. Finally, the growing awareness that this is a heterogeneous disease composed not only of differing phenotypes but also having significant extrapulmonary comorbidities have opened new avenues of research and interdisciplinary collaboration that will further enable us to offer personalized care to patients.

Do we know the minimal clinically important difference (MCID) for COPD exacerbations?

Frequent exacerbations of COPD are associated with accelerated loss of lung function, declining health status, increased mortality, and increased health care costs. Thus, a key objective in the management of COPD is preventing exacerbations or at least reducing their number and severity. When new interventions are examined, their value is sometimes assessed in reference to the minimal clinically important difference (MCID), a theoretical construct that may be defined and estimated numerically in several different ways. There have been limited attempts to calculate the MCID for COPD exacerbations but a figure of 20% reduction in exacerbation frequency is occasionally cited as the "established" MCID from a single manuscript reviewing six clinical trials. Our review suggests that defining and calculating the MCID for COPD exacerbations is problematic, not only because the methodology around developing endpoints for MCIDs is inconsistent, but because the impact of exacerbation reduction is likely to be influenced dramatically by the definitions of exacerbation severity used and the population's baseline status. Reference to current literature shows that at least one other estimate for exacerbation MCID as low as 4%. MCID is sometimes estimated by expert consensus; a review of articles used to shape COPD guidelines shows frequent reference to articles in which interventions yielded exacerbation differences as low as 11%. We find no evidence of an established MCID but suggest that interventions reducing exacerbations by as little as 11% appear to be regarded widely as clinically important.