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The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. Accord-ingly, with National Heart, Lung and Blood Institute support, we initiated the SPIROMICS Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with ≥10 pack-years cigarette smoking, in either Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups 0-2 or with Preserved Ratio Impaired Spirometry (PRISm); and an additional n=40 never-smoker controls. Participants undergo baseline and three-year follow-up visits, each including high-resolution computed tomography; respiratory oscillometry and spirometry (pre- and post-bronchodilator administration), exhaled breath condensate (baseline only); and extensive biospecimen collection, including sputum induction. Symptoms, interim healthcare utilization, and exacerbations are captured every six months via follow-up phone calls. An embedded bronchoscopy sub-study involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.
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BACKGROUND: Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow-up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. METHODS AND RESULTS: The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack-years of smoking history. Cox proportional hazards models and Kaplan-Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47-2.22]; with CVD: HR, 1.92 [95% CI, 1.51-2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events. CONCLUSIONS: COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.
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Doenças Cardiovasculares , Progressão da Doença , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Doenças Cardiovasculares/epidemiologia , Estudos Longitudinais , Idoso de 80 Anos ou mais , Medição de Risco , Incidência , Fatores de Risco , Estudos Prospectivos , Estados Unidos/epidemiologia , Fatores de TempoRESUMO
BACKGROUND: EPIC (Empowering People to Independence in COPD) is a geriatric-palliative care telephonic, nurse coach intervention informed by Baltes' Theory of Successful Aging and adapted from the ENABLE (Educate, Nurture, Advise, Before Life Ends) intervention. EPIC, focused on improving independence, mobility, well-being, and COPD symptoms, has undergone formative and summative evaluation for adults with COPD. METHODS: The primary study aim is to assess the refined EPIC intervention's feasibility and acceptability via a pilot hybrid effectiveness-implementation randomized control trial in community-dwelling older adults with moderate to severe COPD and their family caregivers. The secondary aim is to explore the impact of EPIC on patient and caregiver outcomes. Older adults with COPD and their family caregivers (target N = 60 dyads) will be randomized to EPIC (intervention) or usual COPD care (control). EPIC includes six patient and four family caregiver weekly, telephone-based nurse coach sessions using a manualized curriculum (Charting Your Course), plus three monthly follow-up calls. Feasibility will be measured as completion of EPIC intervention and trial components (e.g., recruitment, retention, data collection). Acceptability will be evaluated using satisfaction surveys and post-study feedback interviews. A blinded data collector will assess exploratory outcomes (e.g., Life-Space mobility, quality of life, caregiver burden, emotional symptoms, loneliness, cognitive impairment, functional status, healthcare utilization) at baseline, 12, and 24 weeks. DISCUSSION: This intervention fills a gap in addressing the geriatrics and palliative care needs and equity for adults with COPD and their family caregivers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05040386.
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Cuidadores , Cuidados Paliativos , Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Idoso , Feminino , Humanos , Masculino , Cuidadores/psicologia , Vida Independente , Tutoria/métodos , Cuidados Paliativos/métodos , Cuidados Paliativos/organização & administração , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/terapia , Doença Pulmonar Obstrutiva Crônica/enfermagem , Telefone , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death worldwide. Cigarette smoke which has approximately 2-3 µg of Cadmium (Cd) per cigarette contributes to the environmental exposure and development and severity of COPD. With the lack of a cadmium elimination mechanism in humans, the contribution of cadmium induced stress to lung epithelial cells remains unclear. Studies on cadmium responsive miRNAs suggest regulation of target genes with an emphasis on the critical role of miRNA-mRNA interaction for cellular homeostasis. Mir-381, the target miRNA in this study is negatively regulated by cadmium in airway epithelial cells. miR-381 is reported to also regulate ANO1 (Anoctamin 1) expression negatively and in this study low dose cadmium exposure to airway epithelial cells was observed to upregulate ANO1 mRNA expression via mir-381 inhibition. ANO1 which is a Ca2+-activated chloride channel has multiple effects on cellular functions such as proliferation, mucus hypersecretion and fibroblast differentiation in inflamed airways in chronic respiratory diseases. In vitro studies with cadmium at a high concentration range of 100-500 µM is reported to activate chloride channel, ANO1. The secretory epithelial cells are regulated by chloride channels like CFTR, ANO1 and SLC26A9. We examined "ever" smokers with COPD (n = 13) lung tissue sections compared to "never" smoker without COPD (n = 9). We found that "ever" smokers with COPD had higher ANO1 expression. Using mir-381 mimic to inhibit ANO1, we demonstrate here that ANO1 expression is significantly (p < 0.001) downregulated in COPD derived airway epithelial cells exposed to cadmium. Exposure to environmental cadmium contributes significantly to ANO1 expression.
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MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Humanos , Cádmio/metabolismo , Anoctamina-1/genética , Anoctamina-1/metabolismo , Células Epiteliais/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , MicroRNAs/metabolismo , RNA Mensageiro/genética , Proteínas de Neoplasias/metabolismo , Transportadores de Sulfato/metabolismo , Antiporters/metabolismoAssuntos
Bronquiectasia , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Bronquiectasia/complicações , Bronquiectasia/diagnóstico por imagem , Tomografia Computadorizada por Raios X , SíndromeRESUMO
Most patients with chronic obstructive pulmonary disease (COPD) have at least one additional, clinically relevant chronic disease. Those with the most severe airflow obstruction will die from respiratory failure, but most patients with COPD die from non-respiratory disorders, particularly cardiovascular diseases and cancer. As many chronic diseases have shared risk factors (eg, ageing, smoking, pollution, inactivity, and poverty), we argue that a shift from the current paradigm in which COPD is considered as a single disease with comorbidities, to one in which COPD is considered as part of a multimorbid state-with co-occurring diseases potentially sharing pathobiological mechanisms-is needed to advance disease prevention, diagnosis, and management. The term syndemics is used to describe the co-occurrence of diseases with shared mechanisms and risk factors, a novel concept that we propose helps to explain the clustering of certain morbidities in patients diagnosed with COPD. A syndemics approach to understanding COPD could have important clinical implications, in which the complex disease presentations in these patients are addressed through proactive diagnosis, assessment of severity, and integrated management of the COPD multimorbid state, with a patient-centred rather than a single-disease approach.
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Multimorbidade , Doença Pulmonar Obstrutiva Crônica , Humanos , Sindemia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Comorbidade , PulmãoRESUMO
OBJECTIVE: The aim of the study is to determine whether aggregate measures of occupational exposures are associated with chronic obstructive pulmonary disease (COPD) outcomes in the Subpopulations and Intermediate Outcome Measures in COPD study cohort. METHODS: Individuals were assigned to six predetermined exposure hazard categories based on self-reported employment history. Multivariable regression, adjusted for age, sex, race, current smoking status, and smoking pack-years determined the association of such exposures to odds of COPD and morbidity measures. We compared these with the results of a single summary question regarding occupational exposure. RESULTS: A total of 2772 individuals were included. Some exposure estimates, including "gases and vapors" and "dust and fumes" exposures resulted in associations with effect estimates over two times the estimated effect size when compared with a single summary question. CONCLUSIONS: Use of occupational hazard categories can identify important associations with COPD morbidity while use of single-point measures may underestimate important differences in health risks.
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Doenças Profissionais , Exposição Ocupacional , Doença Pulmonar Obstrutiva Crônica , Humanos , Exposição Ocupacional/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumar/epidemiologia , Gases , Morbidade , Poeira , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologia , Fatores de RiscoRESUMO
BACKGROUND: Electronic cigarettes (e-cigarettes) are known to cause adverse pulmonary effects, yet paradoxically, the prevalence of e-cigarette use has increased among individuals with chronic lung disease. We assessed the relationship between chronic lung disease and the susceptibility to e-cigarette use in adults and determined if specific behavioral, social, and environmental factors influence this relationship. METHODS: We enrolled adults age ≥ 18 y in Alabama with chronic lung disease from university medical clinics (n = 140) and individuals without chronic lung disease (n = 123, reference group) from January 2020-March 2021. A cross-sectional design was used where we administered questionnaires to collect sociodemographic information and assessed susceptibility to e-cigarette use, exposure to social and environmental factors (ie, advertisements, warning labels, special prices, others' e-cigarette vapors, use of an e-cigarette by others in the home, and visiting a web site or online discussion), and behavioral factors (ie, alcohol and cannabis use). Moderation analyses were conducted to determine if any of these factors would modify the association between chronic lung disease and susceptibility to e-cigarette use. RESULTS: Susceptibility to e-cigarette use was higher among adults without chronic lung disease than among those with chronic lung disease. Noticing e-cigarette warning labels and visiting a web site or online discussion about e-cigarettes were significantly associated with an increased likelihood of susceptibility to using e-cigarettes in both groups. Exposure to e-cigarette vapor from close contacts, special pricing, living with someone who uses e-cigarettes, and cannabis use were significantly associated with an increased likelihood of susceptibility to e-cigarette use in individuals without chronic lung disease. However, our analyses did not indicate a statistically significant interaction between chronic lung disease and any social, environmental, or behavioral factors on susceptibility to e-cigarette use. CONCLUSIONS: Individuals without chronic lung disease were more susceptible to e-cigarette use than those with chronic lung disease. Although the prevalence of some behavioral and environmental factors differed among individuals with and without chronic lung disease, these factors did not moderate the association between chronic lung disease and susceptibility to e-cigarette use. Longitudinal investigations are warranted to better test the temporal relationships between chronic lung disease, substance use, social and environmental factors, and the susceptibility to e-cigarette use among individuals with chronic lung disease to identify prevention strategies for this population.
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Sistemas Eletrônicos de Liberação de Nicotina , Pneumopatias , Produtos do Tabaco , Vaping , Humanos , Adulto , Vaping/efeitos adversos , Estudos Transversais , Pneumopatias/epidemiologia , Pneumopatias/etiologiaRESUMO
Disease stage at the time of diagnosis is the most important determinant of prognosis for lung cancer. Despite demonstrated effectiveness of lung cancer screening (LCS) in reducing lung cancer mortality, early detection continues to elude populations with the highest risk for lung cancer death. Consistent with the national rate, current screening rate in Alabama is dismal at 4.2%. While public awareness of LCS may be a likely cause, there are no studies that have thoroughly evaluated current knowledge of LCS within the Deep South. Therefore, we measured LCS knowledge before and after receiving education delivered by community health advisors (CHAs) among high-risk individuals living in medically underserved communities of Alabama and to determine impact of psychological, demographic, health status, and cognitive factors on rate of lung cancer screening participation. Participants were recruited from one urban county and six rural Black Belt counties (characterized by poverty, rurality, unemployment, low educational attainment, and disproportionate lack of access to health services). One hundred individuals (i) aged between 55 and 80 years; (ii) currently smoke or have quit within the past 15 years; and (iii) have at least a total of 30-pack-year smoking history were recruited. Knowledge scores to assess lung cancer knowledge were calculated. Paired t-test was used to assess pre- and post-knowledge score improvement. Screening for lung cancer was modeled as a function of predisposed factors (age, gender, insurance, education, fatalism, smoking status, and history of family lung cancer). Average age was 62.94 (SD = 6.28), mostly female (54%); mostly current smokers (53%). Most participants (80.85%) reported no family history of cancer. Fatalism was low, with a majority of the participants disagreeing that a cancer diagnosis is pre-destined (67.7%) and that there are no treatments for lung cancer (88.66%). Overall, lung cancer knowledge increased significantly from baseline of 4.64 (SD = 2.37) to 7.61 (SD = 2.26). Of the 100 participants, 23 underwent screening due to lack of access to primary care providers and reluctance of PCPs to provide referral to LCS. Sixty-five percent of those who were screened reported no family history of lung cancer. Regression analysis revealed no significant association between risk factors and the decision to get screened by participants. Our study demonstrates that while CHA delivered education initiatives increases lung cancer screening knowledge, there are significant structural barriers that prohibit effective utilization of LCS which needs to be addressed.
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Neoplasias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/psicologia , Projetos Piloto , Detecção Precoce de Câncer , Saúde Pública , FumarRESUMO
CONTEXT: Early, concurrent palliative care interventions in chronic obstructive pulmonary disease (COPD) are limited. Project EPIC (Early Palliative Care In COPD) is a multiphase mixed methods study working to fill this gap. OBJECTIVES: To conduct a formative and summative evaluation of EPIC, a telephonic nurse coach-led early palliative care intervention for COPD adapted from the ENABLE© intervention in cancer. METHODS: Phase I Formative Evaluation: Patients with moderate-to-very-severe COPD, family caregivers, and pulmonary and palliative care clinicians rated the acceptability and feasibility of EPIC (≥4 out of five on a Likert-scale survey). Phase II Summative Evaluation: Patients and family caregivers in Phase I participated in a pilot of the three month EPIC prototype to evaluate intervention and data collection feasibility (≥70% completion) and to seek qualitative feedback. RESULTS: Phase I Formative Evaluation: Patients (n=10), family caregivers (n=10), pulmonary clinicians (n=6), and palliative care clinicians (n=6) found EPIC acceptable and feasible to support adaptation, while priority early palliative care needs in COPD from our prior research mapped well to the EPIC prototype. Phase II Summative Evaluation: Patients (n=5; ages 49-72, 40% moderate COPD, 40% Black) and their family caregivers (n=5; ages 51-73, 40% Black) completed 100% of EPIC prototype components, including weekly telephone sessions, a one month follow-up call, Advance Directive, palliative care clinic attendance, and 95% of monthly phone data collection sessions. Feedback from participants about EPIC was all positive. CONCLUSION: EPIC was acceptable and feasible in patients with COPD and their family caregivers. Larger feasibility and effectiveness trials are warranted.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Doença Pulmonar Obstrutiva Crônica , Telemedicina , Humanos , Pessoa de Meia-Idade , Idoso , Cuidados Paliativos/métodos , Doença Pulmonar Obstrutiva Crônica/terapia , Cuidadores , Telemedicina/métodosRESUMO
BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts < 100 cells/µL (BEC≤100) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC≤100 phenotype is inadequately characterized, especially in advanced COPD. RESEARCH QUESTION: Are there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes? STUDY DESIGN AND METHODS: We used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC≤100 vs BEC > 100 (BEC100+) in all subjects with COPD (n = 1,414) and GOLD group D subjects (n = 185) not receiving ICS. RESULTS: We identified n = 485 with BEC≤100 (n = 61 GOLD group D) and n = 929 people with BEC100+ (n = 124 GOLD group D). BEC≤100 status was stable at 6 weeks and approximately 52 weeks (intraclass correlations of 0.78 and 0.71, respectively). Compared with BEC100+, BEC≤100 comprised more women, with greater current smoking, and less frequent childhood asthma. Among all analyzed participants, the two BEC-defined subsets showed similar rates of lung function decline (mean slope, BEC≤100 vs BEC100+, -50 vs -39 mL/y; P = .140), exacerbations (0.40 vs 0.36/y; P = .098), subsequent ICS initiation (2.5% vs 4.4%; P = .071), and mortality (7.8% vs 8.4%; P = .715). However, in GOLD group D, people with BEC≤100 showed higher exacerbation rates within 365 days of enrollment (0.62 vs 0.33/y; P = .002) and total follow-up (1.16 vs 0.83/y; P = .014). They also had greater lung function decline (mean slope of -68 mL/y vs -23 mL/y; P = .036) and had greater emphysema at baseline (voxels < 950 Hounsfield units at total lung capacity of 7.46% vs 4.61%; P = .029). INTERPRETATION: In non-ICS-treated GOLD group D COPD, people with BEC≤100 had more baseline emphysema, prospective exacerbations, and lung function decline. Our analysis has identified a particularly vulnerable subpopulation of people with COPD, suggesting the need for studies focused specifically on their therapeutic treatment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01969344; URL: www. CLINICALTRIALS: gov.
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Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Feminino , Humanos , Eosinófilos , Estudos Prospectivos , Corticosteroides/uso terapêutico , Enfisema Pulmonar/tratamento farmacológico , Progressão da Doença , Administração por InalaçãoRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a disease of accelerated aging and is associated with comorbid conditions including osteoporosis and sarcopenia. These extrapulmonary conditions are highly prevalent yet frequently underdiagnosed and overlooked by pulmonologists in COPD treatment and management. There is evidence supporting a role for bone-muscle crosstalk which may compound osteoporosis and sarcopenia risk in COPD. Chest CT is commonly utilized in COPD management, and we evaluated its utility to identify low bone mineral density (BMD) and reduced pectoralis muscle area (PMA) as surrogates for osteoporosis and sarcopenia. We then tested whether BMD and PMA were associated with morbidity and mortality in COPD. METHODS: BMD and PMA were analyzed from chest CT scans of 8468 COPDGene participants with COPD and controls (smoking and non-smoking). Multivariable regression models tested the relationship of BMD and PMA with measures of function (6-min walk distance (6MWD), handgrip strength) and disease severity (percent emphysema and lung function). Multivariable Cox proportional hazards models were used to evaluate the relationship between sex-specific quartiles of BMD and/or PMA derived from non-smoking controls with all-cause mortality. RESULTS: COPD subjects had significantly lower BMD and PMA compared with controls. Higher BMD and PMA were associated with increased physical function and less disease severity. Participants with the highest BMD and PMA quartiles had a significantly reduced mortality risk (36% and 46%) compared to the lowest quartiles. CONCLUSIONS: These findings highlight the potential for CT-derived BMD and PMA to characterize osteoporosis and sarcopenia using equipment available in the pulmonary setting.
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Osteoporose , Doença Pulmonar Obstrutiva Crônica , Sarcopenia , Humanos , Masculino , Feminino , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Força da Mão , Osteoporose/diagnóstico por imagem , Osteoporose/epidemiologia , Osteoporose/complicações , Tomografia Computadorizada por Raios X/efeitos adversos , Morbidade , Músculos , Densidade ÓsseaRESUMO
BACKGROUND: Many persons with a history of smoking tobacco have clinically significant respiratory symptoms despite an absence of airflow obstruction as assessed by spirometry. They are often treated with medications for chronic obstructive pulmonary disease (COPD), but supporting evidence for this treatment is lacking. METHODS: We randomly assigned persons who had a tobacco-smoking history of at least 10 pack-years, respiratory symptoms as defined by a COPD Assessment Test score of at least 10 (scores range from 0 to 40, with higher scores indicating worse symptoms), and preserved lung function on spirometry (ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ≥0.70 and FVC ≥70% of the predicted value after bronchodilator use) to receive either indacaterol (27.5 µg) plus glycopyrrolate (15.6 µg) or placebo twice daily for 12 weeks. The primary outcome was at least a 4-point decrease (i.e., improvement) in the St. George's Respiratory Questionnaire (SGRQ) score (scores range from 0 to 100, with higher scores indicating worse health status) after 12 weeks without treatment failure (defined as an increase in lower respiratory symptoms treated with a long-acting inhaled bronchodilator, glucocorticoid, or antibiotic agent). RESULTS: A total of 535 participants underwent randomization. In the modified intention-to-treat population (471 participants), 128 of 227 participants (56.4%) in the treatment group and 144 of 244 (59.0%) in the placebo group had at least a 4-point decrease in the SGRQ score (difference, -2.6 percentage points; 95% confidence interval [CI], -11.6 to 6.3; adjusted odds ratio, 0.91; 95% CI, 0.60 to 1.37; P = 0.65). The mean change in the percent of predicted FEV1 was 2.48 percentage points (95% CI, 1.49 to 3.47) in the treatment group and -0.09 percentage points (95% CI, -1.06 to 0.89) in the placebo group, and the mean change in the inspiratory capacity was 0.12 liters (95% CI, 0.07 to 0.18) in the treatment group and 0.02 liters (95% CI, -0.03 to 0.08) in the placebo group. Four serious adverse events occurred in the treatment group, and 11 occurred in the placebo group; none were deemed potentially related to the treatment or placebo. CONCLUSIONS: Inhaled dual bronchodilator therapy did not decrease respiratory symptoms in symptomatic, tobacco-exposed persons with preserved lung function as assessed by spirometry. (Funded by the National Heart, Lung, and Blood Institute and others; RETHINC ClinicalTrials.gov number, NCT02867761.).
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Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Antibacterianos/uso terapêutico , Broncodilatadores/uso terapêutico , Volume Expiratório Forçado , Glucocorticoides/uso terapêutico , Glicopirrolato , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Nicotiana/efeitos adversos , Resultado do TratamentoRESUMO
Rationale: There are no pharmacologic agents that modify emphysema progression in patients with chronic obstructive pulmonary disease (COPD). Objectives: To evaluate the efficacy of losartan, an angiotensin receptor blocker, to reduce emphysema progression. Methods: The trial was a multicenter, randomized, placebo-controlled trial conducted between May 2017 and January 2021. Eligible participants were aged ⩾40 years, had moderate to severe airflow obstruction, ⩾10 pack-years of smoking, mild-moderate emphysema on high-resolution computed tomography, and no medical indication for or intolerance of angiotensin receptor blockers. Treatment with losartan 100 mg daily or matching placebo (1:1) was randomly assigned. The primary outcome was emphysema progression on high-resolution computed tomography over 48 weeks. Secondary outcomes included the St George's Respiratory Questionnaire, the modified Medical Research Council dyspnea scale, the COPD Assessment Test, and the Physical Function-Short Form 20a. Measurements and Main Results: A total of 220 participants were enrolled; 58% were men, 19% were African American, and 24% were current smokers. The medians (interquartile ranges) for age were 65 (61-73) years and 48 (36-59) for percent predicted FEV1 after bronchodilator use. The mean (95% confidence interval) percentage emphysema progression was 1.35% (0.67-2.03) in the losartan group versus 0.66% (0.09-1.23) in the placebo group (P = NS). Conclusions: Losartan did not prevent emphysema progression in people with COPD with mild-moderate emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT02696564).
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Enfisema , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Broncodilatadores/uso terapêutico , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Losartan/uso terapêutico , Masculino , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Enfisema Pulmonar/complicações , Enfisema Pulmonar/tratamento farmacológicoRESUMO
Background: Specialist palliative care improves quality of life (QOL), symptom burden, and may prolong survival among patients with advanced lung cancer. Previous trials focused on advanced disease, and less is known about patients across a broad range of stages. Objective: We sought to assess the effect of a nurse-led telephone-based primary palliative care intervention that focused on patients across a broad range of stages. Design, Setting, and Participants: We conducted a multisite randomized controlled trial in the United States involving patients diagnosed within two months with any stage or histology of lung cancer to compare the effects of a telephone-based palliative care intervention delivered by registered nurses trained in primary palliative care versus usual care. Main Outcomes and Measures: The primary outcome was the Functional Assessment of Cancer Therapy-Lung Scale Total Outcome Index (FACT-L TOI), which measures QOL and symptoms. We estimated having 80% power to detect a 5-point change from baseline to three months. Secondary outcome was a change in satisfaction of care, measured by the FAMCARE-P13. Results: A total of 151 patients were enrolled over 30 months. Patients were, on average, male (98%), age 70 years, White (85%), and 36% diagnosed with stage I-II, and 64% had stage III-IV. In comparison to usual care, patients in the nurse-led intervention did not report improvement in QOL from baseline to three months follow-up or demonstrate differences in treatment effect by site or cancer stage: FACT-L TOI 1.03 (95% confidence interval [CI]: -3.98 to 6.04). Satisfaction with care did not significantly improve: 0.66 (95% CI: -2.01 to 3.33). Conclusions: Among patients with newly diagnosed lung cancer, a nurse-led, primary palliative care intervention did not significantly improve QOL, symptom burden, or satisfaction of care. In contrast to several clinical trials demonstrating the effectiveness of delivering specialty palliative care with disease-modifying treatments on QOL among patients with advanced lung cancer, this intervention did not significantly improve QOL among patients with any stage lung cancer. Future research should identify which specific components of primary palliative care improve outcomes for patients newly diagnosed with lung cancer.
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Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias Pulmonares , Humanos , Masculino , Idoso , Cuidados Paliativos , Qualidade de Vida , Papel do Profissional de EnfermagemRESUMO
The etiologies of chronic obstructive pulmonary disease (COPD) remain unclear. Cadmium (Cd) causes both pulmonary fibrosis and emphysema; however, the predictors for Cd exposure and the mechanisms by which Cd causes COPD remain unknown. We demonstrated that Cd burden was increased in lung tissue from subjects with COPD and this was associated with cigarette smoking. Fibrinogen levels increased markedly in lung tissue of patients with smoked COPD compared with never-smokers and control subjects. Fibrinogen concentration also correlated positively with lung Cd load, but inversely with the predicted % of FEV1 and FEV1/FVC. Cd enhanced the secretion of fibrinogen in a cdc2-dependent manner, whereas fibrinogen further mediated Cd-induced peptidylarginine deiminase 2 (PAD2)-dependent macrophage activation. Using lung fibroblasts from CdCl2-treated Toll-like receptor 4 (TLR4) wild-type and mutant mice, we demonstrated that fibrinogen enhanced Cd-induced TLR4-dependent collagen synthesis and cytokine/chemokine production. We further showed that fibrinogen complexed with connective tissue growth factor (CTGF), which in turn promoted the synthesis of plasminogen activator inhibitor-2 (PAI-2) and fibrinogen and inhibited fibrinolysis in Cd-treated mice. The amounts of fibrinogen were increased in the bronchoalveolar lavage fluid (BALF) of Cd-exposed mice. Positive correlations were observed between fibrinogen with hydroxyproline. Our data suggest that fibrinogen is involved in Cd-induced macrophage activation and increases in fibrinogen in patients with COPD may be used as a marker of Cd exposure and predict disease progression.
Assuntos
Cádmio , Doença Pulmonar Obstrutiva Crônica , Animais , Cádmio/toxicidade , Fibrinogênio/efeitos adversos , Humanos , Pulmão/metabolismo , Ativação de Macrófagos , Camundongos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Receptor 4 Toll-LikeRESUMO
PURPOSE OF REVIEW: Current guidelines does not include current or former smokers who do not have spirometric airflow limitation in their diagnostic or therapeutic algorithms for chronic obstructive pulmonary disease (COPD). The purpose of this review is to outline the burden of respiratory morbidity in this population and to discuss the potential utility of their classification as pre-COPD. RECENT FINDINGS: It is increasingly clear that patients with a history of exposure to cigarette smoke or other environmental pollutants may have substantial lung pathology and respiratory impairment even in the absence of airflow limitation, as detected by spirometry. Not all of these patients will develop airflow limitation, but many will have considerable respiratory morbidity and a comparable prognosis to those with classical, spirometrically defined COPD. The use of the term pre-COPD may allow for the identification of these individuals in order to target preventive and earlier therapeutic strategies. SUMMARY: Spirometry is not adequately sensitive to identify many current and former smokers and other exposed populations with significant lung pathology and respiratory symptoms. Though the pathologic processes present in these patients differ, the earlier identification of this pre-COPD population may foster the development of more effective and disease-modifying treatments.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Progressão da Doença , Volume Expiratório Forçado , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , EspirometriaRESUMO
BACKGROUND: Body composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined. RESEARCH QUESTION: Is the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics? STUDY DESIGN AND METHODS: Participants with complete data for at least one visit in the COPDGene study (n = 9,268) and the ECLIPSE study (n = 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation. RESULTS: Both cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1% (95% CI, 2.4%-3.7%; P < .001) in COPDGene, and 2.4% (95% CI, 0.9%-4.0%; P < .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA. INTERPRETATION: Longitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.