Quantitative Assessment Characteristics of Small Pulmonary Vessel Remodelling in Populations at High Risk for COPD and Smokers Using Low-Dose CT.

Purpose: To explore the morphological alterations in small pulmonary vessels in populations at high risk for chronic obstructive pulmonary disease (COPD) and smokers based on multiple computed tomography (CT) quantitative parameters. Patients and Methods: A total of 1969 Three Major Chest Diseases Screening Study participants with available demographic data and smoking history who underwent low-dose chest CT from 2018 to 2020 were included. All subjects were divided into normal, high risk for COPD, and COPD groups according to their pulmonary function test (PFT) results. Furthermore, the three groups were further subdivided into never-smokers, current smokers, and former smokers subgroups according to their smoking history. Quantitative parameters, such as the number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels, were extracted by computer software. Differences in small pulmonary vessel parameters among the groups were compared using two-way ANOVA. Results: The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the group at high risk for COPD were lower than those in the normal group (P<0.05). The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the COPD group were higher than those in the normal group (P<0.05). The number, area of small pulmonary vessels at 6 mm~12 mm subpleura in current smokers with high risk for COPD were higher than those in former smokers with high risk for COPD (P<0.05). Conclusion: The number, area, and volume of small pulmonary vessels in populations at high risk for COPD were decreased. Smoking cessation may impede structural changes in small pulmonary vessels in populations at high risk for COPD.

Bird ownership and pulmonary outcomes apart from hypersensitivity pneumonitis in European older adults.

BACKGROUND: Exposure to birds has been linked with several lung pathologies and especially hypersensitivity pneumonitis, but discordant literature exist on the potential effects of this exposure on other respiratory pathologies. AIM: This study aims to examine the associations between bird ownership and asthma, lung cancer, and chronic obstructive pulmonary disease (COPD) in older European adults. METHODS: A total of 28,109 participants from the Survey of Health, Ageing, and Retirement in Europe were employed and analyzed with multivariate logistic regressions. RESULTS: No association was found with asthma or lung cancer. Bird ownership increased the odds for COPD diagnosis (OR=1.30; 95 % CI: 1.12-1.51) and more so in males (OR=1.53; 95 % CI: 1.25-1.87) after adjustment for demographic, respiratory, lifestyle, and socioeconomic factors. Male bird owners who smoke had an even more increased risk compared to non-smokers, as did those who lived in multi-person households compared to those living alone. CONCLUSION: Bird ownership may be positively associated with COPD in older European males.

Global, Regional, and National Burden of COPD Attributable to Occupational Particulate Matter, Gases, and Fumes, 1990-2019: Findings from the Global Burden of Disease Study 2019.

Background: A study aimed to estimate the burden of Chronic obstructive pulmonary disease (COPD) caused by occupational exposure to particulate matter, gases, and fumes in 204 countries from 1990 to 2019. Methods: Data on the deaths number, age-standardized mortality rates (ASMR), and age-standardized disability-adjusted life years (DALYs) rates (ASDR) of COPD attributable to occupational particulate matter, gases, and fumes were collected from the GBD study 2019. We also investigated the association between the ASDR and SDI. Results: There were 517.7 thousand deaths [95% UI: 413.9 to 634.5] in 2019. The number of deaths increased from 1990 to 2019. The ASMR and ASDR were 6.61 (5.24 to 8.17) and 143.02 (118.56 to 168.69) in 2019, respectively, representing a 46% and 44.5% decrease since 1990. China had the highest number of deaths [200,748.4 (151,897.6 to 260,703.9)], while Nepal had the highest ASMR [39 (27.7 to 50)] and ASDR [724.5 (549 to 894.2)]. Males and females 75-79 and 80-84 years old had the highest number of COPD deaths. A negative correlation was observed when SDI > 0.4, whereas a positive correlation was found when SDI < 0.4. Conclusion: From 1990 to 2019, there was an increase in the number of deaths, but a decline in ASMR and ASDR globally. Besides, there was a heterogeneous burden of COPD attributable to occupational particulate matter, gases, and fumes across regions and countries. It is important to develop and implement strategies to prevent and reduce the burden of COPD attributable to occupational particulate matter, gases, and fumes.

Tobacco Use and Respiratory Symptoms Among Adults: Findings From the Longitudinal Population Assessment of Tobacco and Health (PATH) Study 2014-2016.

INTRODUCTION: We examined the relationship between current tobacco use and functionally important respiratory symptoms. METHODS: Longitudinal cohort study of 16 295 US adults without COPD in Waves 2-3 (W2-3, 2014-2016) of the Population Assessment of Tobacco and Health Study. Exposure-Ten mutually exclusive categories of tobacco use including single product, multiple product, former, and never use (reference). Outcome-Seven questions assessing wheezing/cough were summed to create a respiratory symptom index; cutoffs of ≥2 and ≥3 were associated with functional limitations and poorer health. Multivariable regressions examined both cutoffs cross-sectionally and change over approximately 12 months, adjusting for confounders. RESULTS: All tobacco use categories featuring cigarettes (>2/3's of users) were associated with higher risk (vs. never users) for functionally important respiratory symptoms at W2, for example, at symptom severity ≥ 3, risk ratio for exclusive cigarette use was 2.34 [95% CI, 1.92, 2.85] and for worsening symptoms at W3 was 2.80 [2.08, 3.76]. There was largely no increased symptom risk for exclusive use of cigars, smokeless tobacco, hookah, or e-cigarettes (adjustment for pack-years and marijuana attenuated the cross-sectional e-cigarette association from 1.53(95% CI 0.98, 2.40) to 1.05 (0.67, 1.63); RRs for these products were also significantly lower compared to exclusive use of cigarettes. The longitudinal e-cigarette-respiratory symptom association was sensitive to the respiratory index cutoff level; exclusive e-cigarette use was associated with worsening symptoms at an index cutoff ≥ 2 (RR = 1.63 [1.02, 2.59]) and with symptom improvement at an index cutoff of ≥ 3 (RR = 1.64 [1.04, 2.58]). CONCLUSIONS: Past and current cigarette smoking drove functionally important respiratory symptoms, while exclusive use of other tobacco products was largely not associated. However, the relationship between e-cigarette use and symptoms was sensitive to adjustment for pack-years and symptom severity. IMPLICATIONS: How noncigarette tobacco products affect respiratory symptoms is not clear; some studies implicate e-cigarettes. We examined functionally important respiratory symptoms (wheezing/nighttime cough) among US adults without COPD. The majority of adult tobacco users smoke cigarettes and have higher risk of respiratory symptoms and worsening of symptoms, regardless of other products used with them. Exclusive use of other tobacco products (e-cigarettes, cigars, smokeless, hookah) was largely not associated with functionally important respiratory symptoms and risks associated with their use was significantly lower than for cigarettes. The association for e-cigarettes was greatly attenuated by adjustment for cigarette pack-years and sensitive to how symptoms were defined.

Use of a Smartphone Self-assessment App for a Tobacco-Induced Disease (COPD, Cardiovascular Diseases, Cancer) Screening Strategy and to Encourage Smoking Cessation: Observational Study.

BACKGROUND: Patient self-assessment via a mobile app detects actionable symptoms and has been shown to detect lung cancer relapses early, thereby lengthening survival. OBJECTIVE: The purpose of this study was to assess the incidence of chief symptoms associated with the main tobacco-induced pathologies in both current and ex-smokers through a self-assessment smartphone app and to evaluate the app's capacity to encourage users to quit smoking or reduce consumption, as well as its impact on early lung cancer stages at the time of diagnosis. METHODS: Current and ex-smokers were recruited through an advertising campaign in Sarthe county (France) proposing the free download of a smartphone app. App users were asked to answer 13 questions related to symptoms associated with tobacco-induced diseases (chronic obstructive pulmonary disease [COPD], cardiovascular diseases, cancer). In the event of any positive answer, a message was displayed recommending the user to consult a physician. In addition, they were asked about smoking cessation intention before and after answering these 13 questions. Finally, incidence of stage 1 or 2 lung cancers diagnosed during the launch period of our application was evaluated by comparing data from various sources to those from the same period during the previous year. RESULTS: Of the 5671 users who were eligible for evaluation, an alert was sent to the majority (4118/5671, 72.6%), with a higher incidence for current smokers (2833/3679, 77.0% vs 1298/1992, 65.2%; P<.001). The most frequent symptoms triggering the notifications were fatigue (2023/5671, 35.7%), cough (1658/5671, 29.2%), dyspnea (1502/5671, 26.5%), and persistent chest pain (1286/5671, 22.7%). Of the current smokers, 14.0% (515/3679) showed symptoms suggesting COPD, 15.5% (571/3679) showed symptoms suggesting stable angina, 12.4% (455/3679) probably had lower extremity artery disease, and 6.8% (249/3679) had possible cancer. Of the users, 36.5% (1343/3679) claimed that they thought about quitting smoking, and 48.7% (1795/3679) had thought about reducing their consumption. Surgery-eligible stage 1 and 2 lung cancer incidence was 24% (14/58) during the study period versus 9% (5/54) during the previous year in Sarthe county (P=.04), whereas it remained unchanged in the neighboring county of Maine-et-Loire. CONCLUSIONS: A majority of current and ex-smokers showed worrying symptoms, and the use of a self-assessment smartphone app may drive a majority of smokers toward the intention of smoking cessation or decreasing consumption. A randomized study should be performed to confirm this intention and to support the potential increase of symptomatic lung cancer detection at early, surgery-accessible stages. TRIAL REGISTRATION: ClinicalTrials.gov NCT04048954; https://www.clinicaltrials.gov/ct2/show/NCT04048954.

Pricing air pollution: evidence from short-term exposure to air pollution on hospitalization of acute bronchitis and chronic obstructive pulmonary disease in southwestern China.

Existing evidence suggests that ambient air pollution has serious adverse effects on respiratory diseases, yet there is little direct evidence from China regarding corresponding economic losses. Here we quantified air pollution-related acute health effects and related economic losses of the most common two respiratory diseases in southwestern China, acute bronchitis and chronic obstructive pulmonary disease (COPD). We applied a distributed lag non-linear model to analyse the relationship between ambient air pollutants and hospital admissions of acute bronchitis and COPD, then applied the cost of illness method to explore the attributing economic burden. During the study period, 528 334 and 99 419 hospital admissions of acute bronchitis and COPD, respectively, were recorded. As a result, during the study period the total hospitalization economic losses attributable to air pollution were 486.40 and 254.74 million yuan for acute bronchitis and COPD, respectively, accounting for 0.015% of local gross domestic product. Our research provides intuitive evidence on the health and economic impacts of short-term exposure to air pollution, which is a key basis for the formulation of environmental policies.

The relationship between COPD Assessment Test (CAT) scores and Distress Thermometer (DT) results in COPD patients.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is a condition that affects over 2 million adults in Poland. In recent years, increasing attention has been focused on improving the quality of life of patients with COPD, which includes alleviating their physical discomfort and relates to their mental health. It is therefore critically important to evaluate research tools that can accurately assess the relationship between the physical and mental health of patients with this disease. OBJECTIVE: This aim of the study is to evaluate the relationship between the COPD Assessment Test (CAT) and the Distress Thermometer and Problem List results in COPD patients. MATERIAL AND METHODS: The research evaluated 70 patients with COPD as defined by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) criteria. Demographic data was obtained at baseline. Disease-specific quality of life was assessed using the CAT score, while overall distress was determined using the Distress Thermometer (DT) scale and a modified Problem List. The relationship between the CAT scores and the results of the Distress Thermometer and Problem List was statistically compared. The study was approved by the Bioethics Committee, and all patients provided written informed consent. RESULTS: The mean ± SD age was 69.6±9.05 (range 47-90) years. The average distress level was 4.09±1.95. A significant relationship was established between the CAT score and the results of the Distress Thermometer Scale (p<0.001); patients with higher CAT scores showed the highest level of distress. CONCLUSIONS: CAT was shown to be a simple, fast and clear measurement of disease-specific quality of life and was correlated with levels of distress in patients with COPD. Every patient with COPD should be evaluated using a scale such as the DT to measure their level of psychological distress.

Medical costs of Alpha-1 antitrypsin deficiency-associated COPD in the United States.

BACKGROUND: There are limited data on economic aspects of the genetic variant of chronic obstructive pulmonary disease (COPD) in the context of the more prevalent form of COPD. The objective of this study was to isolate the healthcare resource utilization and economic burden attributable to the presence of a genetic factor among COPD patients with and without Alpha-1 Antitrypsin Deficiency (AATD), twelve months before and after their initial COPD diagnosis. METHODS: Retrospective analysis of OptumLabs® Data Warehouse claims (OLDW; 2000-2017). The OLDW is a comprehensive, longitudinal real-world data asset with de-identified lives across claims and clinical information. AATD-associated COPD cases were matched with up to 10 unique non-AATD-associated COPD controls. Healthcare resource use and costs were assigned into the following categories: office (OV), outpatient (OP), and emergency room visits (ER), inpatients stays (IP), prescription drugs (RX), and other services (OTH). A generalized linear model was used to estimate total pre- and post-index (initial COPD diagnosis) costs from a third-party payer's perspective (2018 USD) controlling for confounders. Healthcare resource utilization was estimated using a negative binomial regression. RESULTS: The study population consisted of 8881 patients (953 cases matched with 7928 controls). The AATD-associated COPD cohort had higher expenditures and use of office visits (OV) and other (OTH) services, as well as OV, outpatient (OP), emergency room (ER), and prescription drugs (RX) before and after the index date, respectively. Adjusted total all-healthcare cost ratios for AATD-associated COPD patients as compared to controls were 2.04 [95% CI: 1.60-2.59] and 1.98 [95% CI: 1.55-2.52] while the incremental cost difference totaled $6861 [95% CI: $3025 - $10,698] and $5772 [95% CI: $1940 - $9604] per patient before and after the index date, respectively. CONCLUSIONS: Twelve months before and after their initial COPD diagnosis, patients with AATD incur higher healthcare utilization costs that are double the cost of similar COPD patients without AATD. This study also suggests that increased costs of AATD-associated COPD are not solely attributable to augmentation therapy use. Future studies should further explore the relationship between augmentation therapy, healthcare resource use, and other AATD-associated COPD expenditures.

Global Burden of Chronic Respiratory Diseases.

Background: Noncommunicable diseases (NCDs) and chronic respiratory diseases (CRDs) are the main causes of mortality and morbidity worldwide. Methods: The main evidences about the NCDs and CRDs burden and related risk factors, from updated international reports and results of original researches, were collected and described in this review. Results: Most recent evidence is available from the Global Burden of Diseases Study (GBD) 2017 reports. There were 3.2 million deaths due to chronic obstructive pulmonary disease (COPD) and 495,000 deaths due to asthma. COPD was the seventh leading cause of years of life lost (YLLs). Overall, prevalent cases of CRDs were 545 million: about 50% for COPD and 50% for asthma. Incident cases of CRDs were 62 million, mostly due to asthma (69%) and COPD (29%). COPD accounted for 81.6 million disability-adjusted life years, asthma for 22.8 million. COPD prevalence of 9.1% has been found in a recent general population sample of North-Eastern Italy, while in Central Italy a 25-year follow-up of a general population sample has shown an increased prevalence of COPD and asthma up to 6.8% and 7.8%, respectively. In Central Italy, a COPD incidence of 8% and an asthma incidence of 3.2% have been found in adult subjects at an 18-year follow-up. Among the risk factors, a relevant role is played by smoking and high body mass index for asthma, while smoking, particulate matter pollution, ambient ozone pollution, occupational exposure to particulate matter, gases and fumes, as well as second-hand smoke, play an important role for COPD. Forecasting the YLLs by 2040 indicates a rising toll from several NCDs due to population growth and aging, with COPD expected to reach the fourth leading cause. Conclusions: Several recent studies and international reports highlighted the huge global health burden of CRDs and other major NCDs, pointing out the need for implementing international collaborations to fight this epidemic trend.

Socioeconomic variations in chronic obstructive pulmonary disease prevalence, diagnosis, and treatment in rural Southwest China.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major and growing cause of morbidity and mortality throughout the world. However, there remains a limited understanding of the association between individual socioeconomic status (SES) and COPD diagnosis and treatment worldwide, including in China. This study investigates socioeconomic variations in prevalence, diagnosis, and treatment of COPD in rural China. METHODS: The present study employed a cross-sectional survey design. The study population was composed of Han majority as well as Na Xi and Bai ethnic minority individuals 35 years of age and older living in Yunnan Province from 2017 to 2019. In total, 7534 individuals consented to participate in the study and complete a structured interview as well as a post-bronchodilator spirometry test. Multivariate logistic regression was used to analyze the association between individual socioeconomic status variables and the prevalence, diagnosis, and treatment of COPD. RESULTS: The age-standardized prevalence of COPD in the present study was 14.3%. Prevalence differed by gender: prevalence for men was 17.1%, versus 11.4% for women (P = 0.0001). Overall, levels of diagnosis and treatment of COPD for participants with COPD were 24.2 and 23.1%, respectively. Multivariate logistic regression indicated that higher educational levels and good access to medical services was associated with an overall lower risk of COPD (P = 0.032 vs. P = 0.018) as well as a higher probability of COPD diagnosis among those with COPD (P = 0.0001 vs. P = 0.002). Participants with COPD with higher educational levels (P = 0.0001) and higher annual household incomes (P = 0.0001) as well as good access to medical services (P = 0.016) were more likely to receive COPD medications and treatment than their counterparts. While Na Xi and Bai participants had a higher probability of having COPD (P = 0.0001), they had a lower probability of having received a diagnosis or treatment for COPD than Han participants (P = 0.0001 vs. P = 0.0012). CONCLUSIONS: Future interventions to further control COPD and improve diagnosis and treatment should focus on ethnic minority communities, and those with low education levels, low annual household incomes, and poor access to medical services.

Cigarette smoke-induced HMGB1 translocation and release contribute to migration and NF-κB activation through inducing autophagy in lung macrophages.

High-mobility group box 1 (HMGB1) shows pro-inflammatory activity in various inflammatory diseases and has been found up-regulated in chronic obstructive pulmonary disease (COPD). Lung macrophages play an important role in airway inflammation and lung destruction in COPD, yet whether HMGB1 is involved in cigarette smoke (CS)-induced lung macrophage dysfunction is unknown. We sought to evaluate the intracellular localization and release of HMGB1 in lung macrophages from COPD patients and CS-exposed mice, and to investigate the role of HMGB1 in regulating autophagy in CS extract (CSE)-treated lung macrophages (MH-S cells). Our results showed that HMGB1 was highly expressed in lung tissues and sera of COPD patients and CS-exposed mice, along with predominantly cytoplasmic exporting from nuclei in lung macrophages. In vitro experiments revealed that CSE promoted the expression, nucleocytoplasmic translocation and release of HMGB1 partly via the nicotinic acetylcholine receptor (nAChR). Blockade of HMGB1 with chicken anti-HMGB1 polyclonal antibody (anti-HMGB1) or glycyrrhizin (Gly) attenuated the increase of LC3B-II and Beclin1, migration and p65 phosphorylation, suggesting the involvement of HMGB1 in autophagy, migration and NF-κB activation of lung macrophages. Hydroxychloroquine (CQ), an autophagy inhibitor, enhanced the increase of LC3B-II but not Beclin1 in CSE or rHMGB1-treated MH-S cells, and inhibition of autophagy by CQ and 3-methyladenine (3-MA) abrogated the migration and p65 phosphorylation of CSE-treated cells. These results indicate that CS-induced HMGB1 translocation and release contribute to migration and NF-κB activation through inducing autophagy in lung macrophages, providing novel evidence for HMGB1 as a potential target of intervention in COPD.

Establishment of rapid risk assessment model for cigarette smoke extract exposure in chronic obstructive pulmonary disease.

Rapid risk assessment models for different types of cigarette smoke extract (CSE) exposure are critical to understanding the etiology of chronic obstructive pulmonary disease. The present study investigated inflammation of cultured tracheal tissues with CSE exposure. Rat trachea rings were isolated, cultured, then exposed to various concentrations of CSE from 3R4 F reference cigarettes for 4 h. Tissue/cellular morphology, ultrastructure, viability and damage, inflammatory cell infiltration, and inflammatory protein levels were measured and compared to untreated controls. Human bronchial epithelial cells (BEAS-2B) exposed to 0 or 300 µg/mL CSE were cocultured with macrophages to assess extent of mobilization and phagocytosis. Endotracheal epithelium cilia densities were significantly reduced with increasing CSE concentrations, while mucous membranes became increasingly disordered; both eventually disappeared. Macrophages became larger as the CSE concentration increased, with microvilli and extended pseudopodium covering their surface, and many primary and secondary lysosomes present in the cytoplasm. Inflammatory cell infiltration also increased with increasing CSE dose, as did intracellular adhesion molecule-1(ICAM-1), interleukin-6(IL-6). The method described here may be useful to qualitatively characterized the effects of the compound under study. Then, we use BEAS-2B cell line system to strength the observation made in the cultured tissues. Probably, an approach to integrate results from both experiments will facilitate its application. These results demonstrate that cultured rat tracheal rings have a whole-tissue structure that undergoes inflammatory processes similar to in vivo tissues upon CSE exposure.

Assessment of lung function in successfully treated tuberculosis reveals high burden of ventilatory defects and COPD.

BACKGROUND: Burden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear. METHODS: We performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5th percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal [LLN]). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC

Prevalence of smoking and reasons for continuing to smoke: a population-based study.

OBJECTIVE: To investigate the prevalence of smoking and the reasons for continuing to smoke among adults in Brazil. METHODS: This was a cross-sectional, population-based study including 1,054 individuals ≥ 40 years of age, residents of the city of Florianopolis, Brazil, of whom 183 were smokers. All of the smokers completed the University of São Paulo Reasons for Smoking Scale (USP-RSS). Depressive symptoms were evaluated with the Hospital Anxiety and Depression Scale, and spirometry was performed to screen for COPD. RESULTS: Of the 183 smokers, 105 (57.4%) were female, 138 (75.4%) were White, and 125 (63.8%) were in a low economic class. The mean level of education among the smokers was 9.6 ± 6.1 years. The mean smoking history was 29 ± 15 pack-years, 59% of the men having a ≥ 30 pack-year smoking history. Approximately 20% of the smokers had COPD, and 29% had depressive symptoms, which were more common in the women. The USP-RSS scores were highest for the pleasure of smoking (PS), tension reduction (TR), and physical dependence (PD) domains (3.9 ± 1.1, 3.6 ± 1.2, and 3.5 ± 1.3, respectively). Scores for the PS, TR, and weight control (WC) domains were significantly higher in women. Smokers with a > 20 pack-year smoking history scored significantly higher on the PD, PS, automatism, and close association (CA) domains. Smoking history was associated with the PD, PS, TR, and CA domains. Depressive symptoms were associated with the PD, social smoking, and CA domains (p = 0.001; p = 0.01; p = 0.09, respectively). Female gender and a low level of education were associated with the PS domain (p = 0.04) and TR domain (p < 0.001). CONCLUSIONS: The prevalence of smoking in our sample was relatively high (17.4%). The USP-RSS domains PS, TR, and WC explain why individuals continue smoking, as do depressive symptoms.

Chronic Obstructive Pulmonary Disease: Evaluation and Management.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death nationally and worldwide. Cigarette smoking is the most common risk factor in the development of COPD. Disease course is variable with some patients having a high degree of obstruction and minimal symptoms, whereas others with better lung function have a greater symptoms burden. The goal of pharmacologic therapy is to minimize symptoms, improve exercise tolerance, and reduce exacerbation risk. No pharmacologic therapy has been shown to improve survival in COPD. Pulmonology referral is recommended for patients with COPD with symptoms despite first-line inhaled therapy, frequent exacerbations, any hospitalizations, or moderate-to-severe disease.

Development and Validation of the Evaluation Platform in COPD (EPIC): A Population-Based Outcomes Model of COPD for Canada.

BACKGROUND: We report the development, validation, and implementation of an open-source population-based outcomes model of chronic obstructive pulmonary disease (COPD) for Canada. METHODS: Evaluation Platform in COPD (EPIC) is a discrete-event simulation model of Canadians 40 years of age or older. Three core features of EPIC are its open-population design (incorporating projections of future population growth, aging, and smoking trends), its incorporation of heterogeneity in lung function decline and burden of exacerbations, and its modeling of the natural history of COPD from inception. Multiple original data analyses, as well as values reported in the literature, were used to populate the model. Extensive face validity and internal and external validity evaluations were performed. RESULTS: The model was internally validated on demographic projections, mortality rates, lung function trajectories, COPD exacerbations, costs and health state utility values, and stability of COPD prevalence over time within strata of risk factors. In external validation, it moderately overestimated the rate of overall exacerbations in 2 independent trials but generated consistent estimates of rate of severe exacerbations and mortality. LIMITATIONS: In its current version, EPIC does not consider uncertainty in the evidence. Several components such as additional (e.g., environmental and occupational) risk factors, treatment, symptoms, and comorbidity will have to be added in future iterations. Predictive validity of EPIC needs to be examined prospectively against future empirical studies. CONCLUSIONS: EPIC is the first multipurpose, open-source, outcome- and policy-focused model of COPD for Canada. Platforms of this type have the capacity to be iteratively updated to incorporate the latest evidence and to project the outcomes of many different scenarios within a consistent framework.

Rural Residence and Poverty Are Independent Risk Factors for Chronic Obstructive Pulmonary Disease in the United States.

RATIONALE: In developing countries, poor and rural areas have a high burden of chronic obstructive pulmonary disease (COPD), and environmental pollutants and indoor burning of biomass have been implicated as potential causal exposures. Less is known about the prevalence of COPD in the United States with respect to urban-rural distribution, poverty, and factors that uniquely contribute to COPD among never-smokers. OBJECTIVES: To understand the impact of urban-rural status, poverty, and other community factors on COPD prevalence nationwide and among never-smokers. METHODS: We studied a nationally representative sample of adults in the National Health Interview Survey 2012-2015, with data linkage between neighborhood data from the U.S. Census's American Community Survey and the National Center for Health Statistics Urban-Rural Classification Scheme. The main outcome was COPD prevalence. MEASUREMENTS AND MAIN RESULTS: The prevalence of COPD in poor, rural areas was almost twice that in the overall population (15.4% vs. 8.4%). In adjusted models, rural residence (odds ratio [OR], 1.23; P < 0.001) and census-level poverty (OR, 1.12; P = 0.012) were both associated with COPD prevalence, as were indicators of household wealth. Among never-smokers, rural residence was also associated with COPD (OR, 1.34; P < 0.001), as was neighborhood use of coal for heating (OR, 1.09; P < 0.001). CONCLUSIONS: In a nationally representative sample, rural residence and poverty were risk factors for COPD, even among never-smokers. The use of coal for heating was also a risk factor for COPD among never-smokers. Future disparities research to elucidate contributors to COPD development in poor and rural areas, including assessments of heating sources and environmental pollutants, is needed.

Enlightening chronic obstructive pulmonary disease through patients' and caregivers' narratives.

PURPOSE: The primary aim of this research was to raise awareness for COPD through real narratives of patients, caregivers, and pulmonologists. The second objective includes providing clinicians new means of caring for and treating patients with COPD. METHODS: Using narrative medicine, testimonies from patients, their caregivers, and clinicians were collected through an online questionnaire enriched by a narrative plot. Narrations were analyzed throughout descriptive statistics and an elaboration of recurring words and expressions. RESULTS: Throughout the project, 350 narratives were collected from 235 patients, 55 caregivers, and 60 physicians. Though a generally neutral reaction had been observed upon diagnosis, COPD had been found to have a high impact on the patients' and caregivers' lives. Metaphors utilized by patients and caregivers were suggestive of fear and panic unlike those utilized by clinicians who usually had a more technical approach. Smoking was a significant concern for not only patients and caregivers but also clinicians. CONCLUSION: Physicians are therefore challenged to find new ways of communicating COPD to raise awareness on this pathology and encourage corrective habits. An important social objective should be the implementation of a health system that is able to optimize patients' and caregivers' lives.

Tartarato de vareniclina para tratamento adjuvante da cessação do tabagismo em pacientes adultos com doença pulmonar obstrutiva crônica ou doenças cardiovasculares / Varenicline tartrate for adjunctive treatment of smoking cessation in adult patients with chronic obstructive pulmonary disease or cardiovascular disease

INTRODUÇÃO: A Doença Pulmonar Obstrutiva Crônica (DPOC) é um estado patológico caracterizado por uma limitação do débito aéreo que não é totalmente reversível. A limitação ventilatória é, geralmente, progressiva e está associada a uma resposta inflamatória anómala dos pulmões à inalação de partículas ou gases nocivos. As doenças cardiovasculares (DCV) são alterações no funcionamento do sistema cardíaco, sendo este responsável por transportar oxigênio e nutrientes necessários às células para essas executarem suas tarefas. O tabagismo está associado a 1.147.037 anos potenciais de vida perdidos por morte prematura (APVP) ao ano, concentrados em infarto agudo do miocárdio (IAM) (239.456), câncer de pulmão (187.865), DPOC (177.329) e AVC (164.618). TECNOLOGIA: Champix® (tartarato de vareniclina). PERGUNTA: O uso do tartarato de vareniclina é eficaz e seguro em adultos fumantes com DCV ou DPOC, quando comparado à terapia de reposição de nicotina ou cloridrato bupropiona para o tratamento adjuvante na interrupção do tabagismo? EVIDÊNCIAS CIENTÍFICAS: No estudo observacional de Melzer et al., 2016, a farmacoterapia foi dispensada a uma minoria de fumantes de alto risco admitidos para DPOC e não estava associada à cessação do tabagismo nos 6 a 12 meses. Em comparação com o adesivo de nicotina, a vareniclina estava associada a uma maior probabilidade de cessação, com diminuição da probabilidade de cessação entre os pacientes tratados com TRN de curta ação. Jimenez Ruiz e colaboradores realizaram uma revisão dos registros clínicos de fumantes com DPOC grave ou muito grave. Neste estudo, a vareniclina não difere em eficácia da bupropiona, medicamento disponibilizado no SUS. A taxa de abstinência contínua nas semanas 9-24 para TRN, bupropiona e vareniclina foram 44%, 60% e 61%, respectivamente. No entanto, a diferença entre as taxas só foi significante na comparação de vareniclina e adesivo de nicotina. O estudo EUROACTION PLUS (EA) avaliou a eficácia de um programa de cardiologia preventiva, que oferece terapia intensiva para cessar o tabagismo, além da vareniclina opcional para fumantes com risco elevado de doença cardiovascular, em comparação com os cuidados habituais na prática geral. Dentre as limitações, ressalta-se que o estudo avaliou a eficácia do programa de tratamento, portanto os resultados de efetividade apresentados não refletem a efetividade do fármaco em si. Um mínimo de 6 meses de abstinência prolongada é recomendado como medida para avaliar os ensaios de cessação do tabagismo. Os resultados foram avaliados no final de 16 semanas apenas. AVALIAÇÃO ECONÔMICA: Como resultado da avaliação econômica, o demandante encontrou uma razão de custo-efetividade incremental que, para cada ex-fumante adicional, a vareniclina gera uma necessidade de investimento de R$ 4.156, 70. Em 24 semanas, quando compara da com a bupropiona, e, um RCEI de R$ 3.111,45, quando comparada com terapia de reposição de nicotina. Após o ajuste realizado pela Secretaria Executiva da Conitec, na população e custo dos medicamentos, a razão de custo-efetividade incremental da comparação entre vareniclina e cloridrato de bupropiona em pacientes com DPOC, aponta que, para cada ex-fumante adicional, a vareniclina gera uma necessidade de investimento de R$ 84.925,20. A RCEI da comparação terapia de reposição de nicotina em pacientes com DPOC aponta que, para cada ex-fumante adicional, a vareniclina gera uma necessidade de investimento de R$ 3.784,78. A RCEI da comparação entre tartarato de vareniclina e cloridrato de bupropiona em pacientes com DC, aponta que, para cada ex-fumante adicional, a vareniclina gera uma necessidade de investimento de R$ 2.621,15. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Ao considerar o cenário, considerando 100% dos pacientes utilizando vareniclina nos cinco anos de impacto, a análise apresentou um AIO de R$ 34 milhões no primeiro ano após a incorporação, chegando a, R$ 181,33 milhões em cinco anos. Após ajustes no modelo, o custo incremental, considerando as mesmas premissas, a AIO foi de 2,7 bilhões em cinco anos, sendo 2,5 bilhões de reais a mais do que o valor apresentado pelo demandante. CONSIDERAÇÕES: Existe incerteza quanto à opção de tratamento mais seguro para pessoas com DCV. Há evidências limitadas sobre o uso de vareniclina em fumantes com DPOC. Faltam dados de manutenção da cessação do tabagismo a longo prazo e de possíveis recaídas. Nenhum estudo randomizado comparou ainda a eficácia da vareniclina com uma combinação de TRN, que, é mais eficaz do que em monoterapia. Existem dados limitados que comparam a eficácia da vareniclina com bupropiona nessa população específica. Sintomas psiquiátricos, incluindo comportamento suicida, foram relatados com vareniclina, mas um nexo de causalidade não foi estabelecido. Eventos cardiovasculares graves foram relatados com vareniclina, mas o tamanho de qualquer risco aumentado é incerto. RECOMENDAÇÃO INICIAL DA CONITEC: A recomendação inicial da Comissão Nacional de Incorporação de Tecnologias no SUS, na 67ª reunião ordinária no dia 13 de junho de 2018, foi por unanimidade, não incorporar o tartarato de vareniclina, entendendo que, faltam evidências robustas de eficácia e segurança no tratamento do tabagismo em pacientes com DPOC ou com doenças cardiovasculares. CONSULTA PÚBLICA: Foram recebidas 62 contribuições, sendo 13 técnico-científicas e 49 contribuições de experiência ou opinião, onde 46% e 64% discordaram da recomendação preliminar da CONITEC, respectivamente. O principal motivo de discordância foi a necessidade de se oferecer mais uma alternativa terapêutica para tratamento do tabagismo. Equivalência terapêutica e eventos adversos foram os principais motivos para concordarem com a recomendação da Conitec. Evidências foram apresentadas e analisadas, porém ainda faltam dados demostrando superioridade da vareniclina em relação aos disponíveis no SUS. DELIBERAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 71ª reunião ordinária da plenária, realizada no dia 07/10/2018, deliberaram por unanimidade recomendar a não incorporação de vareniclina para o tratamento ddo tabagismo em indivíduos com doença cardiovascular ou Doença Pulmonar Obstrutiva Crônica. Foi assinado o Registro de Deliberação nº 380/2018. DECISÃO: A Portaria nº 49, de 16 de outubro de 2017, tornou pública a decisão de não incorporar o tartarato de vareniclina para tratamento adjuvante da cessação do tabagismo em pacientes adultos com doença pulmonar obstrutiva crônica ou doenças cardiovasculares, no âmbito do Sistema Único de Saúde ­ SUS.