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      Molecular mechanism of betulin palliative therapy for chronic obstructive pulmonary disease (COPD) based on P2X7 receptor target of gated ion channel

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          Abstract

          Background

          The aim of this study was to discover the molecular mechanism of betulin palliative therapy for chronic obstructive pulmonary disease (COPD) based on the P2X7 receptor target of gated ion channel.

          Methods

          A COPD mouse model was developed. Changes in pulmonary ventilation function, pulmonary airway and vascular remodeling indicators, inflammatory cells, and inflammatory factors were determined after betulin intervention, and the pathological alterations of lung tissues were detected. An in vitro experimental model was constructed to observe the influence of betulin at varying concentrations on the proliferation of human bronchial epidermal cell line (16-HBE) cells and changes in inflammatory factors in cell supernatant. The expression levels of key proteins in 16-HBE cells transfected with overexpressed or silenced P2X7 genes were determined through quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot.

          Results

          After betulin intervention, pulmonary ventilation function in the 20 mg/kg betulin and 40 mg/kg betulin groups was improved. Levels of white blood cells (WBCs), neutrophils (Ns), tumor necrosis factor (TNF), TNF-ɑ, interleukin (IL)-1β, and IL-6 in the 2 groups also decreased significantly (all P<0.05). The pathological changes in COPD mice were detected. After betulin intervention, the pathological injury of the lung was reduced, the pathological score decreased significantly, and the remodeling indicators of pulmonary airway and pulmonary vessels diminished remarkably (all P<0.05). Betulin had no effect on the proliferation of 16-HBE cells in vitro. After cigarette smoke extract (CSE) stimulation, the rate of survival for 16-HBE cells decreased significantly. After betulin treatment, the survival rate of 16-HBE cells augmented remarkably, and the levels of TNF-ɑ, IL-6, and IL-1β in cell supernatant reduced substantially (all P<0.05). 16-HBE with overexpression and knockdown of P2X7 was constructed. After being treated with betulin, the relative expression levels of messenger RNA (mRNA) of ERK, JNK, rho-associated protein kinase (ROCK), nuclear factor-κB (NF-κB), and p38 in 16-HBE cells with P2X7 overexpression or knockdown were decreased significantly (all P<0.05), but the above indicators were largely unchanged (all P>0.05).

          Conclusions

          Betulin relieved lung pathological injury, ameliorated lung ventilation function, and diminished the level of inflammatory factors in COPD mice, playing a therapeutic role via the P2X7 signaling pathway.

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          Most cited references16

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          Chronic obstructive pulmonary disease.

          Chronic obstructive pulmonary disease (COPD) kills more than 3 million people worldwide every year. Despite progress in the treatment of symptoms and prevention of acute exacerbations, few advances have been made to ameliorate disease progression or affect mortality. A better understanding of the complex disease mechanisms resulting in COPD is needed. Smoking cessation programmes, increasing physical activity, and early detection and treatment of comorbidities are further key components to reduce the burden of the disease. However, without a global political and economic effort to reduce tobacco use, to regulate environmental exposure, and to find alternatives to the massive use of biomass fuel, COPD will remain a major health-care problem for decades to come.
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            Chronic Obstructive Pulmonary Disease and Smoking Status — United States, 2017

            Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD) in the United States; however, an estimated one fourth of adults with COPD have never smoked ( 1 ). CDC analyzed state-specific Behavioral Risk Factor Surveillance System (BRFSS) data from 2017, which indicated that, overall among U.S. adults, 6.2% (age-adjusted) reported having been told by a health care professional that they had COPD. The age-adjusted prevalence of COPD was 15.2% among current cigarette smokers, 7.6% among former smokers, and 2.8% among adults who had never smoked. Higher prevalences of COPD were observed in southeastern and Appalachian states, regardless of smoking status of respondents. Whereas the strong positive correlation between state prevalence of COPD and state prevalence of current smoking was expected among current and former smokers, a similar relationship among adults who had never smoked suggests secondhand smoke exposure as a potential risk factor for COPD. Continued promotion of smoke-free environments might reduce COPD among both those who smoke and those who do not. Data from 418,378 adult respondents to the 2017 BRFSS survey in the 50 states and the District of Columbia (DC) were analyzed. BRFSS is an annual state-based, random-digit–dialed cellular and landline telephone survey of the noninstitutionalized U.S. population aged ≥18 years and is conducted by state health departments in collaboration with CDC.* Response rates for BRFSS are calculated using standards set by the American Association for Public Opinion Research (AAPOR) Response Rate Formula #4. † The response rate is the number of respondents who completed the survey as a proportion of all eligible and likely eligible persons. The median survey response rate for all states and DC in 2017 was 45.9% and ranged from 30.6% to 64.1%. § COPD was defined by an affirmative response to the question “Has a doctor, nurse, or other health professional ever told you that you had chronic obstructive pulmonary disease or COPD, emphysema, or chronic bronchitis?” Persons were considered to have never smoked if they reported never smoking or smoked less than 100 cigarettes during their lifetime. Former smokers had smoked at least 100 cigarettes in their life, but were not current smokers. Current smokers had smoked at least 100 cigarettes and currently smoked some days or every day. Age-specific and age-adjusted ¶ percentages and 95% confidence intervals (CIs) of adults with diagnosed COPD for all respondents and by smoking status were calculated for groups defined by selected sociodemographic characteristics, health characteristics, and state. Comparisons were made between these groups using t-tests with statistical significance set at p 0.3. ¶ Classification based on the National Center for Health Statistics (NCHS) 2013 Urban-Rural Classification Scheme for Counties, which uses 2010 U.S. Census population data and the February 2013 Office of Management and Budget designations of metropolitan statistical area, micropolitan statistical area, or noncore area. https://www.cdc.gov/nchs/data/series/sr_02/sr02_166.pdf. ** Any leisure-time physical activity in the past 30 days. †† Chronic conditions include coronary heart disease (heart attack, angina, or coronary heart disease), stroke, diabetes, cancer, arthritis, kidney disease, and depressive disorder. TABLE 2 Age-adjusted* percentage of adults aged ≥18 years with diagnosed COPD, by smoking status and state — Behavioral Risk Factor Surveillance System, 2017 State Total (N = 418,378) Current smokers (n = 61,855) Former smokers (n = 118,692) Never smoked (n = 237,831) % with COPD (95% CI) % of total (95% CI) % with COPD (95% CI) % of total (95% CI) % with COPD (95% CI) % of total (95% CI) % with COPD (95% CI) Total 6.2 (6.0–6.3) 16.9 (16.6–17.1) 15.2 (14.7–15.7) 23.0 (22.8–23.3) 7.6 (7.3–8.0) 60.1 (59.8–60.4) 2.8 (2.7–2.9) Alabama 10.1 (9.2–11.2) 22.0 (20.5–23.6) 22.7 (19.7–25.9) 22.1 (20.8–23.5) 12.2 (10.2–14.5) 55.9 (54.2–57.6) 4.3 (3.6–5.1) Alaska 6.3 (4.8–8.2) 20.8 (18.2–23.6) 14.0 (9.5–20.1) 26.4 (24.2–28.8) 5.1 (3.6–7.2) 52.8 (49.9–55.7) 3.2 (1.9–5.2) Arizona 5.9 (5.5–6.4) 15.9 (15.1–16.8) 13.9 (12.4–15.6) 23.3 (22.5–24.2) 7.9 (6.7–9.3) 60.8 (59.7–61.9) 2.6 (2.3–3.1) Arkansas 9.3 (8.1–10.8) 23.4 (21.1–26.0) 21.4 (17.7–25.6) 24.3 (22.2–26.6) 12.0 (7.6–18.4) 52.2 (49.5–54.9) 3.6 (2.7–4.7) California 4.4 (3.9–4.9) 11.6 (10.6–12.7) 11.0 (8.7–13.9) 21.7 (20.6–22.8) 6.7 (5.4–8.3) 66.7 (65.3–68.0) 2.2 (1.8–2.7) Colorado 4.2 (3.7–4.7) 14.7 (13.7–15.7) 12.1 (10.2–14.3) 25.4 (24.3–26.5) 4.9 (4.1–5.9) 59.9 (58.7–61.2) 1.7 (1.3–2.1) Connecticut 5.3 (4.7–5.9) 13.4 (12.3–14.6) 14.7 (12.2–17.7) 24.4 (23.3–25.5) 7.2 (5.6–9.3) 62.2 (60.7–63.6) 2.6 (2.0–3.3) DC 5.8 (5.0–6.7) 14.8 (13.5–16.2) 15.5 (11.6–20.4) 19.5 (18.1–21.0) 6.1 (4.7–8.0) 65.7 (63.9–67.5) 2.9 (2.3–3.7) Delaware 7.3 (6.2–8.5) 18.0 (16.2–20.0) 19.2 (15.4–23.6) 23.7 (21.8–25.8) 8.8 (6.7–11.3) 58.2 (55.9–60.5) 2.5 (1.7–3.5) Florida 7.1 (6.3–8.0) 16.8 (15.5–18.1) 15.7 (13.5–18.2) 22.4 (21.2–23.7) 8.2 (6.6–10.3) 60.8 (59.1–62.4) 3.9 (2.9–5.1) Georgia 6.8 (6.1–7.6) 17.8 (16.4–19.2) 16.4 (13.6–19.6) 20.0 (18.8–21.3) 9.4 (6.8–12.9) 62.2 (60.6–63.9) 3.4 (2.8–4.1) Hawaii 3.4 (3.0–3.9) 13.5 (12.4–14.8) 7.8 (5.8–10.5) 25.8 (24.3–27.2) 4.7 (3.7–5.9) 60.7 (59.1–62.3) 1.9 (1.5–2.4) Idaho 4.7 (4.1–5.5) 14.8 (13.4–16.4) 13.1 (10.3–16.5) 23.0 (21.4–24.6) 5.6 (4.3–7.3) 62.2 (60.2–64.2) 2.1 (1.5–2.8) Illinois 6.4 (5.7–7.3) 15.7 (14.4–17.2) 15.2 (12.5–18.4) 22.5 (21.1–23.9) 7.7 (6.1–9.7) 61.8 (60.1–63.5) 2.9 (2.3–3.7) Indiana 8.0 (7.5–8.6) 22.5 (21.5–23.6) 18.3 (16.6–20.1) 23.9 (22.9–24.9) 8.5 (7.5–9.5) 53.6 (52.4–54.8) 3.3 (2.8–3.9) Iowa 5.9 (5.3–6.5) 17.9 (16.8–19.1) 16.4 (14.1–19.0) 24.0 (22.9–25.2) 8.1 (5.8–11.3) 58.0 (56.7–59.4) 2.2 (1.8–2.8) Kansas 6.2 (5.8–6.6) 18.0 (17.3–18.8) 16.3 (14.9–17.8) 23.8 (23.0–24.5) 7.9 (7.1–8.7) 58.2 (57.3–59.1) 2.4 (2.1–2.7) Kentucky 11.3 (10.2–12.5) 25.5 (23.9–27.2) 23.7 (20.7–26.9) 24.6 (23.0–26.1) 11.3 (9.4–13.5) 49.9 (48.2–51.7) 4.3 (3.4–5.4) Louisiana 8.4 (7.4–9.5) 23.8 (22.1–25.6) 16.4 (13.5–19.7) 22.0 (20.5–23.5) 11.2 (9.0–13.9) 54.2 (52.3–56.1) 3.5 (2.8–4.4) Maine 6.5 (5.8–7.3) 18.7 (17.2–20.3) 16.4 (14.1–18.9) 29.0 (27.5–30.5) 8.9 (6.7–11.7) 52.3 (50.6–54.1) 1.9 (1.4–2.5) Maryland 5.4 (4.8–6.0) 14.1 (13.1–15.2) 14.0 (11.7–16.7) 20.9 (19.9–21.9) 6.3 (5.3–7.5) 65.0 (63.7–66.3) 2.7 (2.2–3.3) Massachusetts 5.0 (4.3–5.8) 14.1 (12.7–15.6) 15.2 (11.8–19.3) 23.5 (22.0–25.2) 5.7 (4.5–7.2) 62.4 (60.4–64.2) 1.8 (1.3–2.5) Michigan 8.0 (7.3–8.6) 20.4 (19.3–21.5) 18.6 (16.5–20.9) 25.3 (24.2–26.4) 8.4 (7.3–9.6) 54.3 (53.0–55.6) 3.3 (2.8–4.0) Minnesota 4.0 (3.7–4.4) 14.7 (14.0–15.5) 10.5 (9.1–12.1) 25.6 (24.7–26.4) 5.1 (4.4–5.9) 59.7 (58.7–60.7) 1.6 (1.3–2.0) Mississippi 7.5 (6.6–8.5) 22.9 (21.0–24.9) 15.4 (12.5–18.8) 20.7 (19.1–22.3) 8.9 (6.9–11.3) 56.4 (54.3–58.6) 3.3 (2.5–4.2) Missouri 7.9 (7.1–8.6) 21.6 (20.2–23.2) 19.1 (16.6–21.8) 24.8 (23.4–26.3) 8.6 (7.3–10.0) 53.6 (51.8–55.3) 3.1 (2.5–3.7) Montana 5.7 (4.9–6.5) 18.4 (16.9–20.0) 12.9 (10.3–15.9) 25.8 (24.2–27.5) 7.1 (5.8–8.6) 55.8 (53.9–57.7) 2.3 (1.7–3.0) Nebraska 5.3 (4.8–5.8) 15.9 (14.9–16.9) 14.6 (12.6–16.9) 24.0 (22.9–25.1) 6.4 (5.4–7.5) 60.1 (58.8–61.4) 2.2 (1.8–2.7) Nevada 6.5 (5.5–7.6) 17.5 (15.6–19.6) 14.4 (10.9–18.8) 22.7 (20.8–24.8) 7.9 (5.9–10.5) 59.8 (57.4–62.2) 3.2 (2.3–4.4) New Hampshire 6.0 (5.2–7.0) 17.0 (15.2–19.0) 16.4 (13.0–20.6) 28.3 (26.5–30.1) 7.2 (5.7–9.1) 54.7 (52.5–56.9) 2.5 (1.9–3.3) New Jersey 5.8 (5.1–6.5) 14.1 (12.9–15.4) 12.8 (10.6–15.3) 23.9 (22.6–25.3) 6.3 (5.2–7.7) 62.0 (60.4–63.6) 3.6 (2.8–4.6) New Mexico 5.6 (4.9–6.4) 17.9 (16.4–19.4) 13.2 (10.7–16.3) 22.9 (21.4–24.4) 7.0 (5.5–9.0) 59.3 (57.4–61.0) 2.5 (1.9–3.2) New York 5.0 (4.5–5.5) 14.4 (13.5–15.4) 11.9 (10.2–13.8) 22.1 (21.1–23.2) 5.8 (5.0–6.8) 63.5 (62.2–64.7) 2.8 (2.3–3.3) North Carolina 7.3 (6.4–8.2) 17.5 (16.0–19.1) 16.4 (13.4–20.0) 24.9 (23.3–26.5) 7.7 (6.3–9.4) 57.7 (55.8–59.6) 3.5 (2.8–4.5) North Dakota 4.8 (4.2–5.4) 18.9 (17.6–20.3) 12.5 (10.4–15.1) 25.2 (23.9–26.6) 4.8 (3.9–5.9) 55.8 (54.2–57.5) 1.8 (1.4–2.4) Ohio 7.6 (6.9–8.2) 22.1 (20.8–23.4) 16.7 (14.7–18.8) 23.4 (22.2–24.5) 9.5 (8.1–11.1) 54.6 (53.1–56.0) 2.9 (2.4–3.6) Oklahoma 8.1 (7.3–8.9) 20.5 (19.1–22.0) 17.7 (15.3–20.4) 23.8 (22.5–25.2) 10.6 (9.0–12.5) 55.7 (54.0–57.4) 3.2 (2.6–3.9) Oregon 4.9 (4.3–5.6) 16.7 (15.4–18.1) 12.6 (10.3–15.5) 24.5 (23.2–25.9) 6.2 (4.7–8.0) 58.8 (57.1–60.4) 2.0 (1.5–2.6) Pennsylvania 5.9 (5.3–6.7) 19.7 (18.3–21.1) 11.6 (9.5–14.0) 25.6 (24.2–27.0) 8.8 (7.2–10.7) 54.8 (53.1–56.5) 2.2 (1.7–2.9) Rhode Island 7.0 (6.1–8.1) 15.5 (13.9–17.3) 16.2 (13.0–20.0) 26.7 (25.0–28.4) 10.2 (7.8–13.2) 57.8 (55.7–59.8) 2.5 (1.9–3.4) South Carolina 7.2 (6.6–7.9) 19.7 (18.5–20.9) 16.9 (14.9–19.2) 25.2 (24.1–26.4) 8.0 (6.5–9.8) 55.1 (53.7–56.5) 3.5 (2.9–4.2) South Dakota 4.4 (3.6–5.4) 20.6 (18.5–22.8) 10.2 (7.3–14.2) 25.0 (23.0–27.1) 5.0 (3.8–6.7) 54.5 (52.1–56.8) 2.0 (1.3–2.9) Tennessee 8.9 (8.0–9.8) 23.3 (21.6–25.1) 19.7 (17.2–22.5) 22.8 (21.3–24.3) 9.9 (8.2–11.9) 54.0 (52.0–55.9) 3.7 (2.8–4.8) Texas 4.8 (4.1–5.7) 16.0 (14.5–17.5) 13.3 (10.3–17.1) 19.9 (18.5–21.4) 6.3 (4.7–8.4) 64.1 (62.2–65.9) 2.4 (1.8–3.2) Utah 4.1 (3.6–4.6) 9.0 (8.3–9.8) 12.3 (9.9–15.3) 15.6 (14.7–16.5) 6.1 (5.0–7.4) 75.4 (74.3–76.4) 2.4 (2.0–2.9) Vermont 5.7 (5.1–6.4) 17.3 (15.8–18.9) 17.3 (14.6–20.4) 27.5 (26.0–29.1) 6.2 (5.1–7.5) 55.2 (53.3–57.0) 1.9 (1.5–2.4) Virginia 6.6 (5.9–7.4) 16.8 (15.7–18.0) 16.2 (13.8–19.0) 23.1 (21.9–24.3) 9.1 (6.8–11.9) 60.1 (58.7–61.6) 2.9 (2.4–3.6) Washington 5.4 (5.0–6.0) 13.8 (13.0–14.7) 15.5 (13.3–17.9) 26.3 (25.4–27.3) 7.1 (6.0–8.3) 59.8 (58.7–61.0) 2.0 (1.7–2.4) West Virginia 13.8 (12.7–15.0) 28.1 (26.4–29.9) 25.9 (23.3–28.8) 24.4 (22.9–25.9) 15.1 (12.6–18.0) 47.5 (45.7–49.4) 6.0 (5.0–7.3) Wisconsin 4.7 (4.0–5.5) 16.7 (15.2–18.2) 14.0 (11.1–17.4) 25.0 (23.4–26.6) 4.9 (3.9–6.2) 58.4 (56.5–60.2) 1.9 (1.4–2.6) Wyoming 6.1 (5.3–6.9) 19.2 (17.6–21.0) 12.9 (10.3–16.1) 25.1 (23.5–26.8) 8.7 (7.1–10.6) 55.7 (53.7–57.7) 2.3 (1.8–3.0) Abbreviations: CI = confidence interval; COPD = chronic obstructive pulmonary disease; DC = District of Columbia. * Age-adjusted to the 2000 U.S. standard population aged ≥18 years. FIGURE Age-adjusted* percentage of U.S. adults with chronic obstructive pulmonary disease (COPD), overall and by current or previous smoking status — Behavioral Risk Factor Surveillance System, 2017 Abbreviation: DC = District of Columbia. * Age-adjusted to the 2000 U.S. standard population aged ≥18 years. The figure is a set of four maps showing the age-adjusted percentage of U.S. adults with chronic obstructive pulmonary disease (COPD), overall and among those who currently smoke, those who formerly smoked, and those who have never smoked, according to the Behavioral Risk Factor Surveillance System survey of 2017. Discussion The higher COPD prevalences observed among women, older adults, American Indians/Alaska Natives, adults with less education, those with a history of asthma, and those residing in rural areas were consistent with results from previous studies ( 1 – 3 ). The geographic distribution also was consistent ( 1 ). These patterns were similar among adults who had never smoked. Although smoking tobacco is the main contributor to COPD in the United States, other factors might play a role in the development of COPD among nonsmokers, including secondhand smoke exposure, occupational and environmental exposures, and chronic asthma ( 4 , 5 ). Secondhand smoke exposure, in either childhood or as an adult, has been associated with an increased risk for COPD-associated mortality ( 6 ). The 2006 Surgeon General’s report on secondhand smoke concluded that although the evidence suggested a causal relationship between exposure to secondhand smoke and COPD risk, there was insufficient evidence to state definitively that the relationship is causal ( 7 ). In the current analysis, the geographic distribution of high COPD prevalence was similar for current smokers and adults who never smoked. There is also a strong correlation between state-level prevalences of COPD among adults who never smoked and state-level prevalence of current smoking. This could reflect that in certain regions adults who never smoked might be more likely to be exposed to secondhand smoke. Among the states in the highest quartile for COPD among adults who never smoked, only New Jersey had laws banning smoking in private worksites, restaurants, and bars as of December 31, 2017; the remainder of states in that quartile either had no smoke-free laws or laws banning smoking in only one or two venues.** The findings in this report are subject to at least seven limitations. First, COPD status was based on self-report, not on medical records or diagnostic tests, and might be subject to recall and social desirability biases. Second, physicians might be more likely to diagnose COPD and other smoking-related diseases in states with high smoking rates, whereas COPD might be more likely to remain undiagnosed in states with lower smoking rates. Third, smoking status also was based on self-report and might be subject to social desirability bias. Fourth, because the data were cross-sectional, causality could not be examined. Fifth, e-cigarette use was not examined in this report. There were no other measures of exposure to secondhand smoke or other indoor or outdoor air pollutants or history of respiratory infections, all of which might contribute to COPD risk. Sixth, BRFSS surveys noninstitutionalized adults and does not include adults who live in long-term care facilities, prisons, and other facilities; therefore, findings are not generalizable to those populations. Finally, state BRFSS response rates were relatively low, which might lead to selection bias. Population-based strategies for smoking prevention and control have the potential to decrease the prevalence of COPD in the United States. Such strategies include tobacco product price increases, mass media antismoking campaigns, comprehensive smoke-free laws, and barrier-free access to evidence-based cessation interventions. †† Comprehensive smoke-free laws not only help protect nonsmokers from secondhand smoke exposure, but they can also promote adoption of voluntary smoke-free rules in private settings (e.g., homes and automobiles) and reduce smoking prevalence through increased cessation and decreased initiation. §§ Clinicians can play a key role in increasing access to and use of cessation therapies, including counseling and Food and Drug Administration-approved cessation medications. ¶¶ Current clinical guidelines recommend screening all patients for tobacco use at every visit ( 8 ); however, clinicians should be mindful that not all COPD is necessarily caused by smoking and should use spirometry for diagnosis in patients with COPD symptoms ( 9 ), regardless of their smoking history. Summary What is already known about this topic? Cigarette smoking is the primary risk factor for chronic obstructive pulmonary disease (COPD) in the United States; an estimated one fourth of adults with COPD have never smoked. Higher COPD prevalence has been observed in southeastern and Appalachian states. What is added by this report? Geographic and sociodemographic patterns of COPD prevalence were similar among current smokers, former smokers, and adults who had never smoked. What are the implications for public health practice? Population-based strategies for smoking prevention and control, including comprehensive smoke-free policies, have the potential to decrease COPD prevalence, including among nonsmokers. Clinicians should offer cessation support to patients who smoke and consider COPD in symptomatic patients, regardless of smoking history.
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              Low uptake of palliative care for COPD patients within primary care in the UK

              Mortality and symptom burden from chronic obstructive pulmonary disease (COPD) and lung cancer are similar but there is thought to be an inequality in palliative care support (PCS) between diseases. This nationally representative study assessed PCS for COPD patients within primary care in the UK. This was a cohort study using electronic healthcare records (2004–2015). Factors associated with receiving PCS were assessed using logistic regression for the whole cohort and deceased patients. There were 92 365 eligible COPD patients, of which 26 135 died. Only 7.8% of the whole cohort and 21.4% of deceased patients received PCS. Lung cancer had a strong association with PCS compared with other patient characteristics, including Global Initiative for Chronic Obstructive Lung Disease stage and Medical Research Council Dyspnoea score (whole cohort, lung cancer: OR 14.1, 95% CI 13.1–15; deceased patients, lung cancer: OR 6.5, 95% CI 6–7). Only 16.7% of deceased COPD patients without lung cancer received PCS compared with 56.5% of deceased patients with lung cancer. In patients that received PCS, lung cancer co-diagnosis significantly increased the chances of receiving PCS before the last month of life (1–6 versus ≤1 month pre-death: risk ratio 1.4, 95% CI 1.3–1.7). Provision of PCS for COPD patients in the UK is inadequate. Lung cancer, not COPD, was the dominant driver for COPD patients to receive PCS.
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                Author and article information

                Journal
                Ann Transl Med
                Ann Transl Med
                ATM
                Annals of Translational Medicine
                AME Publishing Company
                2305-5839
                2305-5847
                June 2022
                June 2022
                : 10
                : 12
                : 707
                Affiliations
                [1 ]deptDepartment of Respiration and Intensive Care Unit , The First Affiliated Hospital of Zhengzhou University , Zhengzhou, China;
                [2 ]deptDepartment of Hematology Oncology , The First Affiliated Hospital of Henan University of Traditional Chinese Medicine , Zhengzhou, China;
                [3 ]deptThe First Clinical Medical College , Henan University of Chinese Medicine , Zhengzhou, China;
                [4 ]Department of Respiration and Intensive Care Unit, The First People’s Hospital of Lingbao, Lingbao , China
                Author notes

                Contributions: (I) Conception and design: P Jiao; (II) Administrative support: T Sang; (III) Provision of study materials or patients: Y Wang; (IV) Collection and assembly of data: J Jiao; (V) Data analysis and interpretation: Y Li; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Yameng Li. Department of Respiration and Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Email: 526856303@ 123456qq.com .
                Article
                atm-10-12-707
                10.21037/atm-22-2629
                9279764
                35845496
                86539629-6800-4a4e-b690-8bf562f46571
                2022 Annals of Translational Medicine. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 14 April 2022
                : 20 June 2022
                Categories
                Original Article

                chronic obstructive pulmonary disease (copd),betulin,inflammatory factor,p2x7

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