Effect on Physical Position of Peak Inspiratory Flow in Stable COPD: An Observational Study.

Background: We examined the effect of physical position on peak inspiratory flow (PIF) in patients with chronic obstructive pulmonary disease (COPD) using dry-powder inhalers (DPIs) with low­medium internal resistance (R2) and/or high internal resistance (R5). Methods: This prospective study in stable, ambulatory patients with spirometry-confirmed COPD evaluated the effect of 3 physical positions on maximal PIF achieved. Participants had PIFs of 30-90L/min (R5) or 60-90L/min (R2 DPIs) using the In-Check™ DIAL. PIF was measured in triplicate randomly in 3 positions that patients might be in while using their inhaler (standing, sitting, and semi-upright [supine position with the head of the bed at 45°, neck flexed forward]) against prescribed DPI resistance (R2/R5/both). Correlations between PIF and percentage decline in PIF between positions and differences in participant characteristics with >10% versus ≤10% PIF decline standing to semi-upright were calculated. Results: A total of 76 participants (mean age, 65.2 years) had positional measurements; 59% reported seated DPI use at home. The mean (standard deviation) PIF standing, sitting, and semi-upright was 80.7 (13.4), 77.8 (14.3), and 74.0 (14.5) L/min, respectively, for R2 and 51.1 (9.52), 48.6 (9.84), and 45.8 (7.69) L/min, respectively, for R5 DPIs. PIF semi-upright was significantly lower than sitting and standing (R2; P < 0.0001) and standing (R5; P= 0.002). Approximately half of the participants had >10% decline in PIF from standing to semi-upright. Patient characteristics exceeding the 0.10 absolute standardized difference threshold with the decline in PIF for both the R2 and R5 DPIs were waist-to-hip ratio, modified Medical Research Council dyspnea score, and postbronchodilator percentage predicted forced vital capacity and PIF by spirometry. Conclusions: PIF was significantly affected by physical position regardless of DPI resistance. PIF was highest when standing and lowest when semi-upright. We recommend that patients with COPD stand while using an R2 or R5 DPI. Where unfeasible, the position should be sitting rather than semi-upright. ClinicalTrials.gov identifier NCT04168775.

Questions in Mild Asthma: An Official American Thoracic Society Research Statement.

Background: Patients with mild asthma are believed to represent the majority of patients with asthma. Disease-associated risks such as exacerbations, lung function decline, and death have been understudied in this patient population. There have been no prior efforts from major societies to describe research needs in mild asthma. Methods: A multidisciplinary, diverse group of 24 international experts reviewed the literature, identified knowledge gaps, and provided research recommendations relating to mild asthma definition, pathophysiology, and management across all age groups. Research needs were also investigated from a patient perspective, generated in conjunction with patients with asthma, caregivers, and stakeholders. Of note, this project is not a systematic review of the evidence and is not a clinical practice guideline. Results: There are multiple unmet needs in research on mild asthma driven by large knowledge gaps in all areas. Specifically, there is an immediate need for a robust mild asthma definition and an improved understanding of its pathophysiology and management strategies across all age groups. Future research must factor in patient perspectives. Conclusions: Despite significant advances in severe asthma, there remain innumerable research areas requiring urgent attention in mild asthma. An important first step is to determine a better definition that will accurately reflect the heterogeneity and risks noted in this group. This research statement highlights the topics of research that are of the highest priority. Furthermore, it firmly advocates the need for engagement with patient groups and for more support for research in this field.

Current Perspectives of Pharmacotherapies for COPD.

Pharmacotherapies and avoidance of environmental/inhaled toxins are core to managing COPD. Compared to the drugs available 50 years ago, there has been substantial progress with COPD pharmacotherapies, but gaps in adherence and inhaler use persist. Personalizing inhaled pharmacotherapies is now possible with digital technologies by objectively documenting adherence and guiding inhaler technique. Another means to improve existing pharmacotherapies is through phenotyping and biomarkers. This is especially important considering the heterogeneity of the disease COPD. Blood eosinophils are now a recommended biomarker to guide use of inhaled corticosteroids and biologics in COPD. On the near horizon, we will see new inhaled medications as dual phosphodiesterase inhibitors, drugs to treat basic protein abnormalities as in alpha-1 antitrypsin deficiency that could have remarkable benefits, and biologic drugs targeting specific cell/mediator types in the COPD population. Characterization of COPD phenotypes, as asthma/COPD overlap and comorbid heart disease are vital to understand how to optimize pharmacotherapies. Importantly, we must determine how to optimize current medications; otherwise, we will repeat the same mistakes with new medications. But as we know so well, as we peel one layer of complexity, we encounter many more questions, all the while dedicated to limiting the burden of COPD.

Integrating digital inhalers into clinical care of patients with asthma and chronic obstructive pulmonary disease.

Modernizing inhaled medications through digital technology can help address persistent problems of non-adherence and poor inhaler technique in patients with obstructive lung diseases. With a growing body of supportive clinical studies, advances in digital inhaler sensors and platforms, greater support from payers and healthcare organizations, significant growth with these technologies is expected. While all digital (smart) inhalers record adherence, these are distinguished by their compatibility with commercial inhalers, capabilities to guide inhaler technique, use of patient-reported outcomes, and user-friendliness for both the healthcare professional (HCP) and patient. Due to the complexity and novelty of employing digital inhalers, collaboration with multiple entities within health systems is necessary and a well-planned integration is needed. For HCPs and patients, cybersecurity and privacy are critical, it will require review by each healthcare organization. In the US, some payers reimburse for remote monitoring using digital inhalers, but reimbursement is currently unavailable in other countries. There are several models for remote patient care, as employing an active, ongoing digital interface between the HCP and patient or they may choose to only review data at clinical encounters. Personalization of therapies and feedback are key to success. While digital inhaler malfunction uncommonly occurs, patient attrition over a year is significant. Some patients will be challenged to use digital platforms or have the necessary technology. Additional research is needed to address cost-effectiveness, in vivo accuracy of inspiratory measurement capable devices, ability to teach inhaler technique, their application for monitoring lung function, and lastly real-world adoption and implementation in routine clinical practice.

A Predictive Machine Learning Tool for Asthma Exacerbations: Results from a 12-Week, Open-Label Study Using an Electronic Multi-Dose Dry Powder Inhaler with Integrated Sensors.

Purpose: Machine learning models informed by sensor data inputs have the potential to provide individualized predictions of asthma deterioration. This study aimed to determine if data from an integrated digital inhaler could be used to develop a machine learning model capable of predicting impending exacerbations. Patients and Methods: Adult patients with poorly controlled asthma were enrolled in a 12-week, open-label study using ProAir® Digihaler®, an electronic multi-dose dry powder inhaler (eMDPI) with integrated sensors, as reliever medication (albuterol, 90 µg/dose; 1-2 inhalations every 4 hours, as needed). Throughout the study, the eMDPI recorded inhaler use, peak inspiratory flow (PIF), inhalation volume, inhalation duration, and time to PIF. A model predictive of impending exacerbations was generated by applying machine learning techniques to data downloaded from the inhalers, together with clinical and demographic information. The generated model was evaluated by receiver operating characteristic area under curve (ROC AUC) analysis. Results: Of 360 patients included in the predictive analysis, 64 experienced a total of 78 exacerbations. Increased albuterol use preceded exacerbations; the mean number of inhalations in the 24-hours preceding an exacerbation was 7.3 (standard deviation 17.3). The machine learning model, using gradient-boosting trees with data from the eMDPI and baseline patient characteristics, predicted an impending exacerbation over the following 5 days with an ROC AUC of 0.83 (95% confidence interval: 0.77-0.90). The feature of the model with the highest weight was the mean number of daily inhalations during the 4 days prior to the day the prediction was made. Conclusion: A machine learning model to predict impending asthma exacerbations using data from the eMDPI was successfully developed. This approach may support a shift from reactive care to proactive, preventative, and personalized management of chronic respiratory diseases.

The Eyes Have It-for Idiopathic Pulmonary Fibrosis: a Preliminary Observation.

INTRODUCTION: The disease origins of idiopathic pulmonary fibrosis (IPF), which occurs at higher rates in certain races/ethnicities, are not understood. The highest rates occur in white persons of European descent, particularly those with light skin, who are also susceptible to lysosomal organelle dysfunction of the skin leading to fibroproliferative disease . We had observed clinically that the vast majority of patients with IPF had light-colored eyes, suggesting a phenotypic characteristic. METHODS: We pursued this observation through a research database from the USA Veterans Administration, a population that has a high occurrence of IPF due to predominance of elderly male smokers. Using this medical records database, which included facial photos, we compared the frequency of light (blue, green, hazel) and dark (light brown, brown) eyes among white patients diagnosed with IPF compared with a control group of lung granuloma only (no other radiologic evidence of interstitial lung disease). RESULTS: Light eye color was significantly more prevalent in patients with IPF than in the control group with lung granuloma [114/147 (77.6%) versus 129/263 (49.0%], p < 0.001), indicating that light-colored eyes are a phenotype associated with IPF . CONCLUSION: We provide evidence that light eye color is predominant among white persons with IPF.

Respiratory Symptoms among US Adults: a Cross-Sectional Health Survey Study.

INTRODUCTION: Data collected through ongoing, state-based, cross-sectional health surveys could be used to better understand the contribution of respiratory symptoms to impaired health among the US adult population. METHODS: We used the 2015 Behavioral Risk Factor Surveillance System telephone health survey in four states (Kentucky, Florida, South Carolina, Texas) to describe the relationship between symptoms, associated factors such as tobacco smoking, and health impairments. Self-reported productive cough, shortness of breath (SOB), and dyspnea on exertion (DOE) were categorized as minimal, moderate, or severe. Data were analyzed using multiple logistic regression models with age as a covariate to assess relationships of symptoms with other factors. RESULTS: Among adults ≥ 18 years, respiratory impairment [current asthma, chronic obstructive pulmonary disease (COPD), or a current moderate or severe symptom] occurred in 39.1% of the population. More than half of adults reporting moderate or severe symptoms had not been diagnosed with asthma or COPD, particularly with DOE and productive cough. Subjects were at greater risk of moderate and severe SOB or productive cough with increasing age, prolonged smoking duration (≥ 20 years), being an ever-smoker, or if reporting COPD, current asthma, or any other comorbidity except cancer. Morbid obesity [body mass index (BMI) > 35 kg/m2] was associated with severe DOE at a rate similar to current asthma or COPD (25.6%, 95% CI 20.9-30.3%; 20.8%, 95% CI 16.4-25.1%; 21.3%, 95% CI 17.5-25.1%, respectively); it was the most common cause of DOE. SOB was associated with worse general health impairment and limited ambulation compared with other symptoms. Tobacco smoking prevalence and race varied among states, affecting symptom prevalence. CONCLUSION: In the largest US survey in decades, we provide a current perspective of respiratory symptoms among adults of all ages. While known risk factors were apparent, low-risk persons also frequently reported symptoms and impairments.

Digital Inhalers and Remote Patient Monitoring for Asthma.

Digital inhaler systems, remote patient monitoring, and remote therapeutic monitoring offer great promise as diagnostic tools and therapeutic interventions to improve adherence and inhaler technique for patients with difficult-to-control asthma. In turn, improvements in adherence and inhaler technique may translate into decreasing the need for high side effect treatments such as oral corticosteroids and costly therapies including biologics. Although more clinical trials are needed, studies that use digital inhaler systems to collect objective real-time data on medication-taking behavior via electronic medication monitors and feed this data back to patients on their mobile asthma app, and to health care professionals on the clinician dashboard to counsel patients, show positive outcomes. This article addresses the use of these diagnostic and therapeutic tools in asthma care, how to choose a digital inhaler system, how to teach patients to use the system, strategies for the adoption of these technologies in large health care systems as well as smaller practices, coding and reimbursement, liability concerns, and research gaps.

Measuring Peak Inspiratory Flow in Patients with Chronic Obstructive Pulmonary Disease.

Dry powder inhalers (DPIs) are breath actuated, and patients using DPIs need to generate an optimal inspiratory flow during the inhalation maneuver for effective drug delivery to the lungs. However, practical and standardized recommendations for measuring peak inspiratory flow (PIF)-a potential indicator for effective DPI use in chronic obstructive pulmonary disease (COPD)-are lacking. To evaluate recommended PIF assessment approaches, we reviewed the Instructions for Use of the In-Check™ DIAL and the prescribing information for eight DPIs approved for use in the treatment of COPD in the United States. To evaluate applied PIF assessment approaches, we conducted a PubMed search from inception to August 31, 2021, for reports of clinical and real-life studies where PIF was measured using the In-Check™ DIAL or through a DPI in patients with COPD. Evaluation of collective sources, including 47 applicable studies, showed that instructions related to the positioning of the patient with their DPI, instructions for exhalation before the inhalation maneuver, the inhalation maneuver itself, and post-inhalation breath-hold times varied, and in many instances, appeared vague and/or incomplete. We observed considerable variation in how PIF was measured in clinical and real-life studies, underscoring the need for a standardized method of PIF measurement. Standardization of technique will facilitate comparisons among studies. Based on these findings and our clinical and research experience, we propose specific recommendations for PIF measurement to standardize the process and better ensure accurate and reliable PIF values in clinical trials and in daily clinical practice.

Digital Inhalers for Asthma or Chronic Obstructive Pulmonary Disease: A Scientific Perspective.

Impressive advances in inhalation therapy for patients with asthma and chronic obstructive pulmonary disease (COPD) have occurred in recent years. However, important gaps in care remain, particularly relating to poor adherence to inhaled therapies. Digital inhaler health platforms which incorporate digital inhalers to monitor time and date of dosing are an effective disease and medication management tool, promoting collaborative care between clinicians and patients, and providing more in-depth understanding of actual inhaler use. With advances in technology, nearly all inhalers can be digitalized with add-on or embedded sensors to record and transmit data quantitating inhaler actuations, and some have additional capabilities to evaluate inhaler technique. In addition to providing an objective and readily available measure of adherence, they allow patients to interact with the device directly or through their self-management smartphone application such as via alerts and recording of health status. Clinicians can access these data remotely and during patient encounters, to better inform them about disease status and medication adherence and inhaler technique. The ability for remote patient monitoring is accelerating interest in and the use of these devices in clinical practice and research settings. More than 20 clinical studies of digital inhalers in asthma or COPD collectively show improvement in medication adherence, exacerbation risk, and patient outcomes with digital inhalers. These studies support previous findings about patient inhaler use and behaviors, but with greater granularity, and reveal some new findings about patient medication-taking behaviors. Digital devices that record inspiratory flows with inhaler use can guide proper inhaler technique and may prove to be a clinically useful lung function measure. Adoption of digital inhalers into practice is still early, and additional research is needed to determine patient and clinician acceptability, the appropriate place of these devices in the therapeutic regimen, and their cost effectiveness. Video: Digital Inhalers for Asthma or Chronic Obstructive Pulmonary Disease: A Scientific Perspective (MP4 74535 kb).

Relationship between alpha-1 antitrypsin deficiency and obstructive sleep apnea.

PURPOSE: This study aimed to identify if individuals with mild to severe alpha-1 antitrypsin deficiency (AATD) are at higher risk for developing obstructive sleep apnea (OSA) than the general population. METHODS: A seven-question sleep apnea risk assessment questionnaire, STOP-BAG, was applied to 2338 participant responses from the Alpha-1 Coded Testing Study (ACT) and 4638 participant responses from the Kentucky Behavioral Risk Factor Survey (KyBRFS). Propensity scores were generated from a logistic regression model using continuous variables of age and body mass index (BMI). STOP-BAG scores were analyzed using chi-square analysis on this matched cohort to assess OSA risk in AATD. RESULTS: Self-reported OSA was higher in the KyBRFS cohort (14.5%) than in individuals with mild or severe AATD (11.2%) (p = 0.012). However, a higher percentage of the AATD cohort met clinically meaningful thresholds for STOP-BAG scores ≥ 5 (22.7%) than the KyBRFS cohort (13.0%) (p = 0.001). These differences persisted despite 1:1 propensity score matching on age and BMI to account for differences in baseline characteristics. No statistically significant difference in OSA risk between AATD genotypes was found. CONCLUSION: AATD appears to have higher risk for OSA than the general population. The 11.2% prevalence of diagnosed OSA in the AATD population is much lower than symptom scores would predict. Further studies are needed to validate the possibility that elastin loss is involved in OSA pathogenesis.

Effect of OM-85 BV on reducing bronchiectasis exacerbation in Chinese patients: the iPROBE study.

BACKGROUND: Bronchiectasis is characterized by recurrent infectious exacerbations. No existing data inform preventive strategy for exacerbations beyond chronic macrolides. OM-85 BV, an immunostimulant, has been shown to prevent recurrent respiratory infections. We initiated this 1-year, multi-centered, double-blind, and controlled trial to investigate the PReventive effect of OM-85 BV on Bronchiectasis Exacerbations in Chinese patients (iPROBE). METHODS: Patients with bronchiectasis aged 18 to 75 years, having at least one exacerbation in the past year, were randomized to receive, in addition to any respiratory medications, two courses of 7 mg of OM-85 BV or matching placebo (one capsule orally per day for 10 days a month) for 3 consecutive months, followed by 3 months without treatment. The primary outcomes included the number of acute infectious exacerbations and the time to first exacerbation. Secondary endpoints included patient-reported respiratory outcomes. Safety measures were also assessed. RESULTS: Among the 196 participants, 99 were in the OM-85 BV group and 97 in the placebo group. At week 52, the mean number of acute exacerbations per patient was equal to 0.98 and 0.75, respectively, in the two groups (P=0.14). Difference in the time to first pulmonary exacerbation was not statistically significant (P=0.11). There was no statistically significant difference in any secondary end-points. The safety profile in the two arms was good and the majority of adverse events were mild. CONCLUSIONS: OM-85 BV did not demonstrate protection in decreasing pulmonary exacerbations of bronchiectasis in this trial performed in Chinese patients. It had good safety profile.

Interstitial lung disease in a veterans affairs regional network; a retrospective cohort study.

BACKGROUND: The epidemiology of Interstitial Lung Diseases (ILD) in the Veterans Health Administration (VHA) is presently unknown. RESEARCH QUESTION: Describe the incidence/prevalence, clinical characteristics, and outcomes of ILD patients within the Veteran's Administration Mid-Atlantic Health Care Network (VISN6). STUDY DESIGN AND METHODS: A multi-center retrospective cohort study was performed of veterans receiving hospital or outpatient ILD care from January 1, 2008 to December 31st, 2015 in six VISN6 facilities. Patients were identified by at least one visit encounter with a 515, 516, or other ILD ICD-9 code. Demographic and clinical characteristics were summarized using median, 25th and 75th percentile for continuous variables and count/percentage for categorical variables. Characteristics and incidence/prevalence rates were summarized, and stratified by ILD ICD-9 code. Kaplan Meier curves were generated to define overall survival. RESULTS: 3293 subjects met the inclusion criteria. 879 subjects (26%) had no evidence of ILD following manual medical record review. Overall estimated prevalence in verified ILD subjects was 256 per 100,000 people with a mean incidence across the years of 70 per 100,000 person-years (0.07%). The prevalence and mean incidence when focusing on people with an ILD diagnostic code who had a HRCT scan or a bronchoscopic or surgical lung biopsy was 237 per 100,000 people (0.237%) and 63 per 100,000 person-years respectively (0.063%). The median survival was 76.9 months for 515 codes, 103.4 months for 516 codes, and 83.6 months for 516.31. INTERPRETATION: This retrospective cohort study defines high ILD incidence/prevalence within the VA. Therefore, ILD is an important VA health concern.

A Scoping Review of International Barriers to Asthma Medication Adherence Mapped to the Theoretical Domains Framework.

BACKGROUND: Internationally, adult asthma medication adherence rates are low. Studies characterizing variations in barriers by country are lacking. OBJECTIVE: To conduct a scoping review to characterize international variations in barriers to asthma medication adherence among adults. METHODS: MEDLINE, EMBASE, Web of Science (WOS), and CINAHL were searched from inception to February 2017. English-language studies employing qualitative methods (eg, focus groups, interviews) were selected to assess adult patient- and/or caregiver-reported barriers to asthma medication adherence. Two investigators independently identified, extracted data, and collected study characteristics, methodologic approach, and barriers. Barriers were mapped using the Theoretical Domains Framework and findings categorized according to participants' country of residence, countries' gross national income, and the presence of universal health care (World Health Organization definitions). RESULTS: Among 2942 unique abstracts, we reviewed 809 full texts. Among these, we identified 47 studies, conducted in 12 countries, meeting eligibility. Studies included a total of 2614 subjects, predominately female (67%), with the mean age of 19.1 to 70 years. Most commonly reported barriers were beliefs about consequences (eg, medications not needed for asthma control, N = 29, 61.7%) and knowledge (eg, not knowing when to take medication, N = 27, 57.4%); least common was goals (eg, asthma not a priority, N = 1, 2.1%). In 27 studies conducted in countries classified as high income (HIC) with universal health care (UHC), the most reported barrier was participants' beliefs about consequences (N = 17, 63.3%). However, environmental context and resources (N = 12, 66.7%) were more common in HIC without UHC. CONCLUSION: International adherence barriers are diverse and may vary with a country's sociopolitical context. Future adherence interventions should account for trends.

A population-based estimate of the health care burden of obstructive sleep apnea using a STOP-BAG questionnaire in South Carolina.

STUDY OBJECTIVES: Population based estimates of obstructive sleep apnea (OSA) frequency and health impact are incomplete. The aim of this study was to determine the prevalence of risk factors for physician and sleep study diagnosed OSA among individuals in a state-based surveillance program. METHODS: Using questions inserted into the 2016 (n = 5,564) and 2017 (n = 10,884) South Carolina Behavioral Risk Factor Surveillance System of the Centers for Disease Control and Prevention, we analyzed the prevalence of physician diagnosed OSA and associated comorbidities. The validated STOP-BANG questionnaire without neck circumference (STOP-BAG) defined populations at moderate risk (score 3-4) and high risk (score 5-7). Statistical analysis using weighted prevalence and means and their 95% confidence intervals (CI) thus reflect population estimates of disease burden. RESULTS: The population-based prevalence of physician diagnosed OSA in South Carolina was 9.7% (95% CI: 9.0-10.4). However, the populations with moderate risk (18.5%, 95% CI: 17.3-19.8) and high risk (25.5%, 95% CI: 23.9-27.1) for OSA, as determined by the STOP-BAG questionnaire, were much higher. Compared to those at low risk for OSA, those at high risk were more often diagnosed with coronary heart disease, stroke, asthma, skin cancer, other cancers, chronic obstructive pulmonary disease, arthritis, depression, kidney disease, and diabetes (all P < .001). CONCLUSIONS: OSA is common and strongly associated with major comorbidities. As such, this public health crisis warrants more diagnostic and therapeutic attention. The STOP-BAG questionnaire provides a public health platform to monitor this disease.

Procalcitonin for Antibiotic Prescription in Chronic Obstructive Pulmonary Disease Exacerbations: Systematic Review, Meta-Analysis, and Clinical Perspective.

The 2020 Global Initiative for Obstructive Lung Disease report indicates that the blood biomarker procalcitonin (PCT) may assist in decision-making regarding the initiation of antibiotics for chronic obstructive pulmonary disease (COPD) exacerbations. PCT is an acute-phase reactant that increases in response to inflammation and infection, and has been studied in various bacterial infections for initiation and de-escalation of antibacterials. The purpose of this systematic review and meta-analysis was to evaluate the strength of the data on the use of PCT to guide antibiotic prescription in COPD exacerbations. Among the randomized clinical trials included in our meta-analysis, almost all of which were conducted exclusively in the hospital setting. PCT was found to decrease overall antibiotic exposure in COPD exacerbations by 2.01 days (p = 0.04), while no apparent effects were found on clinical outcomes (length of hospital stay, p = 0.88; treatment failure p = 0.51; all-cause mortality p = 0.28). However, the majority of blood PCT levels in COPD exacerbations were below the manufacturer-recommended cutoff for antibiotics, and the use of this marker was associated with worse outcomes in the intensive care setting. Further, based on additional sensitivity analysis excluding studies with high risk of bias or with converted outcome value, the effect of PCT on antibiotic duration in RCTs was no longer significant (MD = -1.88 days, 95% CI [-3.95, 0.19] days, p = 0.08, and MD = -1.72 days, 95% CI [-4.28, 0.83] days, p = 0.19, respectively). Our review and analysis does not support the use of PCT to guide antibiotic prescription in COPD exacerbations.

A Systematic Review and Meta-Analysis of Sputum Purulence to Predict Bacterial Infection in COPD Exacerbations.

The 2020 Global Initiative for Obstructive Lung Disease (GOLD) Report highlights the importance of sputum purulence in the decision to prescribe antibiotics for acute exacerbations. The purpose of this systematic review and meta-analysis was to evaluate the strength of literature supporting inclusion of sputum purulence in criteria utilized to evaluate if antimicrobials are indicated in acute COPD exacerbation. A total of 6 observational studies met inclusion criteria for this meta-analysis. Sputum purulence was defined by visual assessment of color, either subjectively by providers and/or patients or by a colored chart, where green or yellow sputum was considered purulent. Four of the studies were primarily conducted in hospitalized patients, one in the emergency department, and one in the primary care setting. Five studies relied upon expectorated sputum and one used bronchoscopy to obtain sputum samples for bacterial cultures. Compared with mucoid sputum, purulent sputum had a significantly higher probability of positive bacterial culture results (RR = 2.14, 95%CI [1.25, 3.67], p = 0.006, moderate quality). For sensitivity analysis, after removal of studies losing 2 or more points from the New Castle-Ottawa scale, the effect value remained statistically significant. This systematic review and meta-analysis showed a moderate level of evidence that purulent sputum during COPD exacerbation, as defined by yellow or green color, is associated with a significantly higher probability of potentially pathogenic bacteria, supporting GOLD report and NICE recommendations.