Hemodialysis as an Effective Treatment for Combined Amlodipine and Metformin Overdose: A Case Report and Literature Review.

The combined toxicity of amlodipine and metformin is a rarely reported phenomenon in the literature. The management varies depending on the clinical status of the patient. We present a case that was managed successfully with the early initiation of hemodialysis.

A Rare Case of Cyclophosphamide-Induced Posterior Reversible Encephalopathy Syndrome in a Patient With Acute Lupus Nephritis Flare.

Posterior reversible encephalopathy syndrome (PRES) is a syndrome encompassing both clinical and radiological manifestations with white matter vasogenic edema predominantly of the posterior and parietal lobes of the brain. It may accompany several medical conditions including immunosuppressive/cytotoxic drugs. We present a case of cyclophosphamide-induced PRES in a patient treated for acute lupus flare with biopsy-proven lupus nephritis. A 23-year-old African American female presented with non-specific symptoms over a six-month period on a medical background of systemic lupus erythematosus and biopsy-proven focal lupus nephritis class III on hydroxychloroquine, prednisone, and mycophenolate mofetil for which she was non-compliant. She was borderline hypertensive, tachycardic, saturating well on ambient air, and alert and oriented. Laboratory workup revealed electrolyte imbalance, elevated serum urea, creatinine, and B-type natriuretic peptide, low serum complements, and elevated double-stranded DNA (dsDNA) with negative lupus anticoagulant, anti-cardiolipin, and B2 glycoprotein antibody. Chest imaging revealed cardiomegaly with small pericardial effusion, left pleural effusion, and trace atelectasis, with no deep vein thrombosis on Doppler ultrasound. She was admitted to the intensive care unit for lupus flare with severe hyponatremia and was continued on mycophenolate mofetil, hydroxychloroquine, and prednisone 60 mg for induction therapy as well as intravenous fluids. Hyponatremia resolved, and blood pressure was controlled. She became fluid overloaded and anuric, with pulmonary edema and worsening hypoxic respiratory failure not responding to diuretic challenges. Daily hemodialysis was started, and she was intubated. Prednisone was tapered down, mycophenolate was switched to cyclophosphamide/mesna. She became agitated, restless, and confused, with waxing and waning consciousness and hallucinations. She was continued on bi-weekly cyclophosphamide for induction therapy. After the second dose of cyclophosphamide, her mentation worsened. Non-contrast MRI showed extensive bilateral cerebral and cerebella deep white matter high-intensity signals suggestive of PRES, which was new compared to one year prior. Cyclophosphamide was held and her mentation improved. She was successfully extubated and discharged to a rehabilitation center. The exact pathophysiological mechanism of PRES is not known. Endothelial damage and vasogenic edema have been hypothesized as possible mechanisms. Severe anemia, fluid overload, and renal failure are some of the causes of endothelial dysfunction and vasogenic edema with disruption of the blood-brain barrier, which were found in our patient, but repeated dosing of cyclophosphamide worsened her condition. Discontinuation of cyclophosphamide led to a significant improvement and complete reversal of her neurologic symptoms, implying that prompt recognition and management of PRES is vital to prevent permanent damage and even death in these patients.

Fractional exhaled nitric oxide and mortality in asthma and chronic obstructive pulmonary disease in a national cohort aged 40 years and older.

BACKGROUND: Little is known about Fractional concentration of exhaled Nitric Oxide (FeNO) as a predictor of mortality in persons with asthma or chronic obstructive pulmonary disease (COPD). OBJECTIVE: This study tested the hypotheses that FeNO level ≥ 25 ppb was associated with mortality in a national cohort of persons with asthma or COPD age ≥ 40 years. METHODS: In the 2007-2012 National Health and Nutrition Examination Survey (NHANES), FeNO was measured using an electrochemical sensor. Mortality was determined through 2015 using linkage to the National Death Index. Weighted Cox proportional hazards survival analysis was performed taking the complex survey design into account using STATA V.17. RESULTS: Among the 611 participants with current asthma, 5.16% died during the follow-up period. FeNO ≥ 25 ppb was associated with a hazard ratio (HR) of 0.20, (p = 0.006, 95% CI:0.068-0.618) alone or with little change after controlling for confounding variables. Due to effect modification, the analysis was repeated in persons with and without a history of emergency department (ED) visit for asthma in the previous year. In 522 persons without ED visits, FeNO ≥ 25 ppb was significantly associated with mortality HR 0.094, 95 CI 0.034-0.26, p < 0.001. In 83 persons with ED visits no significant association remained after controlling for all confounders. (Six persons were omitted from this analysis due to missing data on confounders in the extended regression model.) Among 614 with COPD, FeNO ≥ 25 ppb was not associated with mortality. CONCLUSION: In persons with current asthma at baseline, FeNO ≥ 25 ppb was associated with reduced hazard of mortality during follow up among those with no history of ED visits in the previous year. No significant association of FeNO with mortality was seen in persons with COPD.

Pulmonary Embolism and Chronic Superior Vena Cava Occlusion Complicating Central Line-Associated Venous Thromboembolism in a Sickle Cell Disease Patient.

Sickle cell disease (SCD), the most common genetic disorder globally, is often associated with an increased risk of venous thromboembolic events (VTE). Many of these patients have central lines placed for the purposes of repeated medication administration, blood transfusions, and blood draw, further increasing the risk of VTE. Given the non-specific presentation of VTE and pulmonary embolism, as well as the risk of mortality if interventions are delayed, a high index of suspicion is required for early diagnosis of the condition. We report the case of a 35-year-old woman with SCD and a port-a-cath in place who presented with extensive upper extremity and intrathoracic VTE with associated pulmonary embolism and chronic superior vena cava (SVC) occlusion. We also discuss the peculiarities of the clinical manifestations and management of VTE and pulmonary embolism in the setting of SCD based on the evidence from existing literature.

Extended-Spectrum Beta-Lactamase- and Carbapenemase-Producing Enterobacteriaceae Family of Bacteria from Diarrheal Stool Samples in Northwest Ethiopia.

Background: Resistance among the commensal flora is a serious threat because they are highly populated ecosystems like the gut, maybe a source of extraintestinal infections. Infections due to extended-spectrum beta-lactamase (ESBL)- and carbapenemase (CPM)-producing Enterobacteriaceae family of bacteria impose a major global issue because they are usually resistant to multiple antimicrobial agents. Data on the fecal ESBL- and CPM-producing group of bacteria in developing countries including Ethiopia are limited mainly due to resource constraints. Thus, this study aimed to determine the prevalence of multidrug-resistant (MDR)-, ESBL-, and CPM-producing Enterobacteriaceae family of bacteria from diarrheal stool samples at the University Hospital, Northwest Ethiopia. Materials and Methods: A hospital-based cross-sectional study was conducted involving a total of 384 study participants having gastrointestinal complaints from January to April 2019. A diarrheal stool sample was aseptically collected and inoculated on a MacConkey agar plate. After getting pure colonies, biochemical and antimicrobial susceptibility testing was done following standard microbiological techniques. ESBL production was screened using ceftazidime and cefotaxime and confirmed using a combined disk diffusion test. Carbapenemases were screened by meropenem disk and confirmed by the modified carbapenem inactivation method. Data were checked, cleaned, and entered using Epi Info version 7.1 and transferred to SPSS version 20 for analysis. Result: A total of 404 Enterobacteriaceae groups of bacteria were isolated from 384 diarrheal stool samples. The overall prevalence of fecal MDR-, ESBL-, and CPM-producing group of Enterobacteriaceae was 196 (48.5%), 66 (16.3%), and 4 (1%), respectively. Of the total ESBL-producing Enterobacteriaceae, E. coli (41/66 (62.1%)) and K. pneumoniae (18/66 (27.3%)) were the most predominant isolates. One half of CPE has been observed in Citrobacter species and the rest in E. coli (25%) and P. vulgaris (25%). Conclusion and Recommendation. Finding the high rate of ESBL-producing Enterobacteriaceae and CPE requires strict infection control measures and careful selection of empirical therapy in the study area. Therefore, active surveillance with large sample size and better infection prevention control is needed.

Clinical Characteristics and Predictors of Mortality in Minority Patients Hospitalized with COVID-19 Infection.

OBJECTIVES: To identify the early mortality predictors in minority patients hospitalized with coronavirus disease 2019 (COVID-19). DESIGN: Demographics, presenting characteristics, admission laboratory data, ICU admission, and mortality data were collected from 200 consecutively hospitalized patients with COVID-19. RESULTS: The mean (SD) age was 58.9 (15.1) years, 121(60.5%) were men, 143 (71.5%) were African Americans, and 33 (16.5%) were Latino. Common presenting symptoms were cough 130 (65.0%), shortness of breath 129 (64.5%), and fever 121 (60.5%). One or more comorbid illness occurred in 171 (85.5%) and common comorbidities were hypertension (130 (65.2%)), diabetes (100 (50.0%)) and chronic kidney disease (60 (30.0%)). Of the 200 patients, 71 (35.5%) were treated in the ICU, 47 (24.2%) received mechanical ventilation, 45 (22.5%) died, and 155(77.5%) patients discharged home alive. The non-survivors were significantly older and had elevated markers of inflammation, coagulation, and acute organ damage on presentation. Age ≥ 65 years (odds ratio (OR), 3.78; 95% CI, 1.74-8.22; P = .001), lactate dehydrogenase level > 400 IU/L (OR, 9.1; 95% CI, 2.97-28.1; p < 0.001), C-reactive protein > 20 mg/dl (OR, 5.56; 95%CI, 1.84-16.8; p < 0.001), ferritin > 2000 ng/ml (OR, 5.42; 95%CI, 1.63-17.9; p = 0.006), creatinine kinase > 1000 iu/l (OR, 3.57; 95% CI, 1.23 10.3; p = 0.019), procalcitonin > 2.5 ng/ml (OR, 4.21; 95% CI, 1.47-12.0; p = 0.007), D-dimer level > 3.0 µg/ml (OR,10.9; 95% CI, 3.33-36.2; p = < 0.001), creatinine > 2 mg/dl (OR, 4.5; 95% CI, 1.29-15.8; P = 0.018) at admission were associated independently with increases risk of in-hospital mortality. CONCLUSION: Patients of advanced age that present with elevated biomarkers of inflammation, coagulation, and end-organ damage were at higher risk of mortality.

Absence of Antibody Reponses and Severe COVID-19 in Patients on Hemodialysis Following mRNA Vaccination.

Inpatient dialysis patients cannot isolate, resulting in a higher rate of coronavirus disease 2019 (COVID-19) infections, with increased severity and higher mortality rate [1]. We present 2 African American dialysis patients who developed severe COVID-19 infections after vaccination. Both patients had not mounted antibody response to the COVID-19 vaccine or to hepatitis B vaccination.

Geographic Heterogeneity in Influenza and Pneumonia Mortality in Hispanic Americans.

(1) Background: Influenza and pneumonia (IP) is a leading cause of death in the US. The hypothesis was tested that the mortality rate differential between Hispanic whites (HW) and non-Hispanic whites (NHW) from IP varied by geographic region in the US. (2) Methods: The CDC database for multiple causes of death between 1999-2018 was used for this study. For ages 25-84, age-adjusted mortality rates per 100,000 (AAMR) for IP were computed by Hispanic ethnicity in whites for 10 Health & Human Services (HHS) regions and for urbanization levels in HHS Region 2. (3) Results: AAMR for IP was 13.76 (13.62-13.9) in HW and 14.91 (14.86-14.95) in NHW (rate ratio 1.08). Among HHS regions, rates were generally lower in HW than in NHW with the major exception of HHS Region 2. The rate there was 21.78 (21.24-22.33) in HW, 36.5% greater (p < 0.05) than that in NHW of 15.71 (15.56-15.86). In large central metro areas of Region 2, the rate was 27.10 (26.36-27.83) in HW compared to 19.78 (19.47-20.09) in NHW. (4) Conclusion: The difference in AAMR from IP between HW and NHW varied by region and urbanization with much higher rates for HW than NHW only in metropolitan areas of New York and New Jersey.

Geographic Variation in Racial Disparities in Mortality From Influenza and Pneumonia in the United States in the Pre-Coronavirus Disease 2019 Era.

BACKGROUND: In 2018, influenza and pneumonia was the eighth leading cause of death in the United States. Since 1950, non-Hispanic blacks (NHBs) have experienced higher rates of mortality than non-Hispanic whites (NHWs). Previous studies have revealed geographic variation in mortality rates by race. The identification of areas with the greatest disparity in influenza and pneumonia mortality may assist policymakers in the allocation of resources, including for the coronavirus disease 2019 pandemic. RESEARCH QUESTION: Does geographic variation in racial disparity in influenza and pneumonia mortality exist? STUDY DESIGN AND METHODS: The Centers for Disease Control and Prevention database for Multiple Cause of Death between 1999 and 2018 for NHB and NHW decedents ≥ 25 years of age with a Tenth Revision of the International Statistical Classification of Diseases and Related Health Problems code for influenza (J09-J11) and pneumonia (J12-J18) was used. Age-adjusted mortality rates (AAMRs) with 95% CIs were computed by race for Health & Human Services (HHS) regions and urbanization in NHBs and NHWs. RESULTS: In 1999 through 2018, there were 540,476 deaths among NHBs and NHWs 25 to 84 years of age. AAMRs were higher in NHBs than NHWs in each age group and in seven of 10 HHS regions. The greatest disparity was in HHS regions 2 (New York and New Jersey) and 9 (Arizona, California, Hawaii, and Nevada). In HHS region 2, NHBs (24.6; 95% CI, 24.1-25.1) were more likely to die than NHWs (15.7; 95% CI, 15.6-15.9). Similarly, in region 9, NHBs (23.2; 95% CI, 22.7-23.8) had higher mortality than NHWs (16.1; 95% CI, 15.9-16.2). Within these regions, disparities were greatest in the core of major metropolitan areas. A very high AAMR in NHBs was noted in large, central metropolitan areas of region 2: 28.2 (95% CI, 27.6-28.9). INTERPRETATION: In 1999 through 2018, the NHB-NHW disparity in AAMRs from influenza and pneumonia was greatest in central metropolitan areas of HHS regions 2 and 9.

Riociguat in the Treatment of Chronic Thromboembolic Pulmonary Hypertension: An Evidence-Based Review of Its Place in Therapy.

Chronic thromboembolic pulmonary hypertension (CTEPH) is classified as group-4 pulmonary hypertension caused by organized thrombi in pulmonary arteries and vasculopathy in nonoccluded areas leading to right heart failure and death. In addition to chronic anticoagulation therapy, each patient with CTEPH should receive treatment assessment starting with evaluation for pulmonary endarterectomy (PEA), which is the guideline recommended treatment. There is increasing experience with balloon pulmonary angioplasty (BPA) for inoperable patients; this option, like PEA, is reserved for specialized centers with expertise in this treatment method. Inoperable patients are candidates for targeted drug therapy. Riociguat remains the only approved medical therapy for CTEPH patients deemed inoperable or with persistent pulmonary hypertension after PEA. The role of riociguat therapy preoperatively or in tandem with BPA is currently under investigation. The purpose of this review is to evaluate the safety and efficacy of riociguat in the treatment of CTEPH.

Identifying Clinical and Research Priorities in Sickle Cell Lung Disease. An Official American Thoracic Society Workshop Report.

Background: Pulmonary complications of sickle cell disease (SCD) are diverse and encompass acute and chronic disease. The understanding of the natural history of pulmonary complications of SCD is limited, no specific therapies exist, and these complications are a primary cause of morbidity and mortality.Methods: We gathered a multidisciplinary group of pediatric and adult hematologists, pulmonologists, and emergency medicine physicians with expertise in SCD-related lung disease along with an SCD patient advocate for an American Thoracic Society-sponsored workshop to review the literature and identify key unanswered clinical and research questions. Participants were divided into four subcommittees on the basis of expertise: 1) acute chest syndrome, 2) lower airways disease and pulmonary function, 3) sleep-disordered breathing and hypoxia, and 4) pulmonary vascular complications of SCD. Before the workshop, a comprehensive literature review of each subtopic was conducted. Clinically important questions were developed after literature review and were finalized by group discussion and consensus.Results: Current knowledge is based on small, predominantly observational studies, few multicenter longitudinal studies, and even fewer high-quality interventional trials specifically targeting the pulmonary complications of SCD. Each subcommittee identified the three or four most important unanswered questions in their topic area for researchers to direct the next steps of clinical investigation.Conclusions: Important and clinically relevant questions regarding sickle cell lung disease remain unanswered. High-quality, multicenter, longitudinal studies and randomized clinical trials designed and implemented by teams of multidisciplinary clinician-investigators are needed to improve the care of individuals with SCD.

Disparities in Sarcoidosis Mortality by Region, Urbanization, and Race in the United States: A Multiple Cause of Death Analysis.

PURPOSE: Sex, race/ethnicity, and geographic disparities in sarcoidosis-associated mortality were assessed for the most recent period. METHODS: US data for multiple causes of death for 1999-2016 were used to determine numbers of deaths and age-adjusted rates for sarcoidosis as an underlying or a contributing cause of death using International Classification of Diseases, 10th Revision code D86 for Hispanics, non-Hispanic blacks, and non-Hispanic whites. RESULTS: For persons of all ages in the United States in 1999-2016, there were a total of 28,923 sarcoidosis-associated deaths. In 2008-2016, 9112 deaths had sarcoidosis as the underlying cause (56%) compared with 16,129 with sarcoidosis listed as any cause. Age-adjusted annual death rates per 100,000 were 5.7 (95% confidence interval [CI], 5.6-5.8) for females and 4.1 (95% CI, 4.0-4.2) for males. Age-adjusted annual death rates were 1.5 (95% CI, 1.4-1.6) for Hispanics and 5.4 (95% CI, 5.3-5.4) for non-Hispanics. Rates in non-Hispanic blacks were 8 times those in non-Hispanic whites. Among females, the highest rate was in non-Hispanic blacks in the East-Central division. Between 1999-2007 and 2008-2016, rates increased most in non-Hispanic white males (52.5%) and least in non-Hispanic black females (5.8%). CONCLUSIONS: Sarcoidosis-related multiple cause of death mortality rates were highest in females and in non-Hispanic blacks, and they varied geographically.

Disparities in Sepsis Mortality by Region, Urbanization, and Race in the USA: a Multiple Cause of Death Analysis.

PURPOSE: To assess gender, race/ethnicity, and geographic disparities in sepsis-associated mortality. MATERIALS AND METHODS: The US data for multiple causes of death (MCOD) for years 2013-2016 were used to determine numbers of deaths and age-adjusted rates for sepsis as underlying or contributing cause of death using the International Classification of Diseases-10 (ICD-10) codes for non-Hispanic blacks (NHB) and whites (NHW) aged 15 years and older. RESULTS: There were a total of 746,725 sepsis-associated deaths. Among females, age-adjusted death rate for NHB was 88.6 (95% CI 87.8-89.3) and for NHW, 55.4 (95% CI 55.1-55.6). Among males, age-adjusted death rate for NHB was 115.2 (95% CI 114.1-116.3) and for NHW, 69.5 (95% CI 69.2-69.8). Rates were generally higher in divisions of the south region (West South Central in NHB). Within the South, NHW and NHB who resided in non-metropolitan areas had the highest rates, while the lowest were in suburban metropolitan areas. CONCLUSIONS: Sepsis-related MCOD mortality rates were highest in males, in NHB, in the South region, and, within the South, non-metropolitan areas.

Abnormal Ventilation-Perfusion Scan Is Associated with Pulmonary Hypertension in Sickle Cell Adults.

Pulmonary hypertension (PH) in adults with sickle cell disease (SCD) is associated with early mortality. Chronic thromboembolic PH (CTEPH) is an important complication and contributor to PH in SCD but is likely underappreciated. Guidelines recommend ventilation-perfusion (V/Q) scintigraphy as the imaging modality of choice to exclude CTEPH. Data on V/Q scanning are limited in SCD. Our objective was to compare the performance of V/Q scanning with that of CT pulmonary angiography (CTPA) and to report clinical outcomes associated with abnormal V/Q findings. Methods: Laboratory data, echocardiography, 6-min-walk testing, V/Q scanning, CTPA, and right heart catheterization (RHC) were prospectively obtained. High-probability and intermediate-probability V/Q findings were considered to be abnormal. Included for analysis were 142 SCD adults (aged 40.1 ± 13.7 y, 83 women, 87% hemoglobin SS) in a stable state enrolled consecutively between March 13, 2002, and June 8, 2017. Results: V/Q results were abnormal in 65 of 142 patients (45.8%). CTPA was positive for pulmonary embolism in 16 of 60 (26.7%). RHC confirmed PH (mean pulmonary artery pressure ≥ 25 mmHg) in 46 of 64 (71.9%), of whom 34 (73.9%) had abnormal V/Q findings. Among those without PH by RHC (n = 18), 2 of 18 patients had abnormal V/Q findings. Thirty-three patients had a complete dataset (V/Q scanning, CTPA, and RHC); 29 of 33 had abnormal RHC findings, of whom 26 had abnormal V/Q findings, compared with 11 who had abnormal CTPA findings. There was greater concordance between V/Q findings and RHC (κ-value = 0.53; P < 0.001) than between CTPA and RHC (κ-value = 0.13; P = 0.065). The sensitivity and specificity for V/Q scanning was 89.7% and 75.0%, respectively, whereas CTPA had sensitivity of 37.3% and specificity of 100%. Abnormal V/Q finding swere associated with hemodynamic severity (mean pulmonary artery pressure, 35.2 ± 9.6 vs. 26.9 ± 10.5 mm Hg, P = 0.002; transpulmonary gradient, 21.5 ± 9.7 vs. 12.16 ± 11 mmHg, P = 0.005; and pulmonary vascular resistance, 226.5 ± 135 vs. 140.7 ± 123.7 dynes⋅s⋅cm-5, P = 0.013) and exercise capacity (6-min-walk distance, 382.8 ± 122.3 vs. 442.3 ± 110.6 m, P < 0.010). Thirty-four deaths were observed over 15 y. All-cause mortality was higher in the abnormal-V/Q group (21 [61.8%]) than in the normal-V/Q group (13 [38.2%]) (log-rank test, P = 0.006; hazard ratio, 2.54). Conclusion: V/Q scanning is superior to CTPA in detecting thrombotic events in SCD. Abnormal V/Q findings are associated with PH, worse hemodynamics, lower functional capacity, and higher mortality. Despite high sensitivity in detecting CTEPH, V/Q scanning is underutilized. We recommend the use of V/Q scanning in the evaluation of dyspnea in adult SCD patients given the important implications toward management.

Does Low FEV1 in Addition to Fixed Ratio and/or Lower Limit of Normal of FEV1/FVC Improve Prediction of Mortality in COPD? The NHANES-III-linked-mortality Cohort.

PURPOSE: There is presently an ongoing debate on the relative merits of suggested criteria for spirometric airway obstruction. This study tests the null hypothesis that no superiority exists with the use of fixed ratio (FR) of forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC) < 0.7 versus less than lower limit predicted (LLN) criteria with or without FEV1 <80% predicted in regards to future mortality. METHODS: In 1988-1994 the Third National Health and Nutrition Examination Survey (NHANES III) measured FEV1 and FVC with mortality follow-up data through December 31, 2011. For this survival analysis 7472 persons aged 40 and over with complete data formed the analytic sample. RESULTS: There were a total of 3554 deaths. Weighted Cox proportional hazards regression revealed an increased hazard ratio in persons with both fixed ratio and lower limit of normal with a low FEV1 (1.79, p < 0.0001), in those with fixed ratio only with a low FEV1 (1.77, p < 0.0001), in those with abnormal fixed ratio only with a normal FEV1 (1.28, p < 0.0001) compared with persons with no airflow obstruction (reference group). These remained significant after adjusting for demographic variables and other confounding variables. CONCLUSIONS: The addition of FEV1 < 80% of predicted increased the prognostic power of the fixed ratio <0.7 and/or below the lower limit of predicted criteria for airway obstruction.

Riociguat use in sickle cell related chronic thromboembolic pulmonary hypertension: A case series.

Adults with sickle cell disease can develop pulmonary hypertension from a multitude of etiologies. Classified as WHO Group 5, there are no therapies approved for the treatment of sickle cell disease-pulmonary hypertension. Thromboembolic disease is prevalent in sickle cell disease and can lead to pulmonary hypertension. The only approved medical therapy for chronic thromboembolic pulmonary hypertension is riociguat. We report the experience, safety and tolerability of riociguat use in a series of sickle cell disease patients with chronic thromboembolic pulmonary hypertension.

Mortality Related to Chronic Obstructive Pulmonary Disease and Co-morbidities in the United States, A Multiple Causes of Death Analysis.

Chronic obstructive pulmonary disease (COPD) mortality based on the underlying cause of death (UCOD) underestimates disease burden. We aimed to determine the current COPD mortality rate, trends and the distribution of co-morbidities using United States (US) multiple-cause of death (MCOD) records. All 38,905,575 death certificates of decedents aged ≥45 years in the United States were analyzed for 1999-2015. COPD was defined by ICD-10 codes J40-J44 and J47 based either on the UCOD or up to 20 contributing causes coded. Annual age-standardized COPD death rates were computed by age, gender and race/ethnicity for those with any mention of COPD. In 2015, COPD was mentioned in 11.59% (292,572 deaths) in MCOD, compared to 11.13% (243,617 deaths) in 1999, a 4% increase. However, it was reported as the UCOD for only 5.56% and 4.97% in 2015 and 1999 respectively, an 11% increase. The most common UCOD in subjects with any mention of COPD was respiratory disorders in 49% of males and 55% of females. The relative change in death rates differed between MCOD and UCOD. For example, among non-Hispanic white females aged 65-74 years the UCOD rate per 100,000 (95% CI) decreased from 163 (160-166) to 147 (145-150), average annual percent decrease (AAPD) -0.26, while the MCOD rate decreased from 308 (304-311) to 263 (260-267), AAPD -0.87. Statistics based on UCOD understated the burden of COPD in the United States. MCOD rates were twice as high as UCOD rates. The relative change in death percent or rates differed between MCOD and UCOD. MCOD analysis should be repeated periodically to help evaluate the burden of COPD-related mortality.