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Background The low-dose CT (≤3 mGy) screening report of 1000 Early Lung Cancer Action Program (ELCAP) participants in 1999 led to the International ELCAP (I-ELCAP) collaboration, which enrolled 31 567 participants in annual low-dose CT screening between 1992 and 2005. In 2006, I-ELCAP investigators reported the 10-year lung cancer-specific survival of 80% for 484 participants diagnosed with a first primary lung cancer through annual screening, with a high frequency of clinical stage I lung cancer (85%). Purpose To update the cure rate by determining the 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening in the expanded I-ELCAP cohort. Materials and Methods For participants enrolled in the HIPAA-compliant prospective I-ELCAP cohort between 1992 and 2022 and observed until December 30, 2022, Kaplan-Meier survival analysis was used to determine the 10- and 20-year lung cancer-specific survival of participants diagnosed with first primary lung cancer through annual low-dose CT screening. Eligible participants were aged at least 40 years and had current or former cigarette use or had never smoked but had been exposed to secondhand tobacco smoke. Results Among 89 404 I-ELCAP participants, 1257 (1.4%) were diagnosed with a first primary lung cancer (684 male, 573 female; median age, 66 years; IQR, 61-72), with a median smoking history of 43.0 pack-years (IQR, 29.0-60.0). Median follow-up duration was 105 months (IQR, 41-182). The frequency of clinical stage I at pretreatment CT was 81% (1017 of 1257). The 10-year lung cancer-specific survival of 1257 participants was 81% (95% CI: 79, 84) and the 20-year lung cancer-specific survival was 81% (95% CI: 78, 83), and it was 95% (95% CI: 91, 98) for 181 participants with pathologic T1aN0M0 lung cancer. Conclusion The 10-year lung cancer-specific survival of 80% reported in 2006 for I-ELCAP participants enrolled in annual low-dose CT screening and diagnosed with a first primary lung cancer has persisted, as shown by the updated 20-year lung cancer-specific survival for the expanded I-ELCAP cohort. © RSNA, 2023 See also the editorials by Grenier and by Sequist and Olazagasti in this issue.
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Neoplasias Pulmonares , Feminino , Masculino , Humanos , Idoso , Seguimentos , Estudos Prospectivos , Estimativa de Kaplan-Meier , PesquisadoresRESUMO
Lung cancer (LC) is the most common cause of cancer death, with 75% of cases being diagnosed in late stages. This study aimed to determine potential miRNAs as biomarkers for the early detection of LC in chronic obstructive pulmonary disease (COPD) cases. Ninety-nine patients were included, with registered clinical and lung function parameters followed for 6 years. miRNAs were determined in 16 serum samples from COPD patients (four with LC and four controls) by next generation sequencing (NGS) at LC diagnosis and 3 years before. The validation by qPCR was performed in 33 COPD-LC patients and 66 controls at the two time points. Over 170 miRNAs (≥10 TPM) were identified; among these, miR-224-5p, miR-206, miR-194-5p, and miR-1246 were significantly dysregulated (p < 0.001) in COPD-LC 3 years before LC diagnosis when compared to the controls. The validation showed that miR-1246 and miR-206 were differentially expressed in COPD patients who developed LC three years before (p = 0.035 and p = 0.028, respectively). The in silico enrichment analysis showed miR-1246 and miR-206 to be linked to gene mediators in various signaling pathways related to cancer. Our study demonstrated that miR-1246 and miR-206 have potential value as non-invasive biomarkers of early LC detection in COPD patients who could benefit from screening programs.
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Neoplasias Pulmonares , MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Humanos , Perfilação da Expressão Gênica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética , Detecção Precoce de CâncerRESUMO
Fibroblast activation includes differentiation to myofibroblasts and is a key feature of organ fibrosis. The Notch pathway has been involved in myofibroblast differentiation in several tissues, including the lung. Here, we identify a subset of collagen-expressing cells in the lung that exhibit Notch3 activity at homeostasis. After injury, this activation increases, being found in αSMA-expressing myofibroblasts in the mouse and human fibrotic lung. Although previous studies suggest a contribution of Notch3 in stromal activation, in vivo evidence of the role of Notch3 in lung fibrosis remains unknown. In this study, we examine the effects of Notch3 deletion in pulmonary fibrosis and demonstrate that Notch3-deficient lungs are protected from lung injury with significantly reduced collagen deposition after bleomycin administration. The induction of profibrotic genes is reduced in bleomycin-treated Notch3-knockout lungs that consistently present fewer αSMA-positive myofibroblasts. As a result, the volume of healthy lung tissue is higher and lung function is improved in the absence of Notch3. Using in vitro cultures of lung primary fibroblasts, we confirmed that Notch3 participates in their survival and differentiation. Thus, Notch3 deficiency mitigates the development of lung fibrosis because of its role in mediating fibroblast activation. Our findings reveal a previously unidentified mechanism underlying lung fibrogenesis and provide a potential novel therapeutic approach to target pulmonary fibrosis.
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Colágeno/metabolismo , Pulmão/metabolismo , Miofibroblastos/metabolismo , Fibrose Pulmonar/metabolismo , Receptor Notch3/deficiência , Actinas/metabolismo , Animais , Bleomicina , Diferenciação Celular , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Progressão da Doença , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miofibroblastos/patologia , Fenótipo , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Fibrose Pulmonar/fisiopatologia , Receptor Notch3/genéticaRESUMO
In December 2019, an outbreak of severe acute respiratory syndrome associated to SARS-CoV2 was reported in Wuhan, China. To date, little is known on histopathological findings in patients infected with the new SARS-CoV2. Lung histopathology shows features of acute and organising diffuse alveolar damage. Subtle cellular inflammatory infiltrate has been found in line with the cytokine storm theory. Medium-size vessel thrombi were frequent, but capillary thrombi were not present. Despite the elevation of biochemical markers of cardiac injury, little histopathological damage could be confirmed. Viral RNA from paraffin sections was detected at least in one organ in 90% patients.
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COVID-19/diagnóstico , Pulmão/diagnóstico por imagem , Pandemias , SARS-CoV-2 , Tomografia Computadorizada por Raios X/métodos , Biópsia , COVID-19/epidemiologia , Humanos , Espanha/epidemiologiaRESUMO
PURPOSE: Lung cancer risk models optimise screening by identifying subjects at highest risk, but none of them consider emphysema, a risk factor identifiable on baseline screen. Subjects with a negative baseline low-dose CT (LDCT) screen are at lower risk for subsequent diagnosis and may benefit from risk stratification prior to additional screening, thus we investigated the role of radiographic emphysema as an additional predictor of lung cancer diagnosis in participants with negative baseline LDCT screens of the National Lung Screening Trial. METHODS: Our cohorts consist of participants with a negative baseline (T0) LDCT screen (n=16 624) and participants who subsequently had a negative 1-year follow-up (T1) screen (n=14 530). Lung cancer risk scores were calculated using the Bach, PLCOm2012 and Liverpool Lung Project models. Risk of incident lung cancer diagnosis at the end of the study and number screened per incident lung cancer were compared between participants with and without radiographic emphysema. RESULTS: Radiographic emphysema was independently associated with nearly double the hazard of lung cancer diagnosis at both the second (T1) and third (T2) annual LDCT in all three risk models (HR range 1.9-2.0, p<0.001 for all comparisons). The number screened per incident lung cancer was considerably lower in participants with radiographic emphysema (62 vs 28 at T1 and 91 vs 40 at T2). CONCLUSION: Radiographic emphysema is an independent predictor of lung cancer diagnosis and may help guide decisions surrounding further screening for eligible patients.
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Neoplasias Pulmonares/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Doses de Radiação , Estudos Retrospectivos , Medição de RiscoAssuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/patologia , Idoso , Tomografia Computadorizada por Raios X , Nódulo Pulmonar Solitário/diagnóstico por imagem , Pulmão/diagnóstico por imagem , AdultoRESUMO
Each of the pathological stages (I-IIIa) of surgically resected non-small-cell lung cancer has hidden biological heterogeneity, manifested as heterogeneous outcomes within each stage. Thus, the finding of robust and precise molecular classifiers with which to assess individual patient risk is an unmet medical need. Here, we identified and validated the clinical utility of a new prognostic signature based on three proteins (BRCA1, QKI, and SLC2A1) to stratify early-stage lung adenocarcinoma patients according to their risk of recurrence or death. Patients were staged according to the new International Association for the Study of Lung Cancer (IASLC) staging criteria (8th edition, 2018). A test cohort (n = 239) was used to assess the value of this new prognostic index (PI) based on the three proteins. The prognostic signature was developed by Cox regression with the use of stringent statistical criteria (TRIPOD: Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis). The model resulted in a highly significant predictor of 5-year outcome for disease-free survival (p < 0.001) and overall survival (p < 0.001). The prognostic ability of the model was externally validated in an independent multi-institutional cohort of patients (n = 114, p = 0.021). We also demonstrated that this molecular classifier adds relevant information to the gold standard TNM-based pathological staging, with a highly significant improvement of the likelihood ratio. We subsequently developed a combined PI including both the molecular and the pathological data that improved the risk stratification in both cohorts (p ≤ 0.001). Moreover, the signature may help to select stage I-IIA patients who might benefit from adjuvant chemotherapy. In summary, this protein-based signature accurately identifies those patients with a high risk of recurrence and death, and adds further prognostic information to the TNM-based clinical staging, even when the new IASLC 8th edition staging criteria are applied. More importantly, it may be a valuable tool for selecting patients for adjuvant therapy. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Adenocarcinoma de Pulmão/química , Proteína BRCA1/análise , Biomarcadores Tumorais/análise , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Transportador de Glucose Tipo 1/análise , Imuno-Histoquímica , Neoplasias Pulmonares/química , Proteínas de Ligação a RNA/análise , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/terapia , Idoso , Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Transportador de Glucose Tipo 1/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Proteínas de Ligação a RNA/genética , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Espanha , Texas , Fatores de TempoRESUMO
RATIONALE: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) document has modified the grading system directing pharmacotherapy, but how this relates to the previous one from 2015 and to comorbidities, hospitalizations, and mortality risk is unknown. OBJECTIVES: The aim of this study was to evaluate the changes in the GOLD groups from 2015 to 2017 and to assess the impact on severity, comorbidities, and mortality within each group. METHODS: We prospectively enrolled and followed, for a mean of 5 years, 819 patients with chronic obstructive pulmonary disease (84% male) in clinics in Spain and the United States. We determined anthropometrics, lung function (FEV1%), dyspnea score (modified Medical Research Council scale), ambulatory and hospital exacerbations, and the body mass index, obstruction, dyspnea, and exercise capacity (BODE) and Charlson indexes. We classified patients by the 2015 and 2017 GOLD ABCD system, and compared the differential realignment of the same patients. We related the effect of the reclassification in BODE and Charlson distribution as well as chronic obstructive pulmonary disease and all-cause mortality between the two classifications. MEASUREMENTS AND MAIN RESULTS: Compared with 2015, the 2017 grading decreased by half the proportion of patients in groups C and D (20.5% vs. 11.2% and 24.6% vs. 12.9%; P < 0.001). The distribution of Charlson also changed, whereas group D was higher than B in 2015, they become similar in the 2017 system. In 2017, the BODE index and risk of death were higher in B and D than in A and C. The mortality risk was better predicted by the 2015 than the 2017 system. CONCLUSIONS: Compared with 2015, the GOLD ABCD 2017 classification significantly shifts patients from grades C and D to categories A and B. The new grading system equalizes the Charlson comorbidity score in all groups and minimizes the differences in BODE between groups B and D, making the risk of death similar between them.
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Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Corticosteroides/uso terapêutico , Idoso , Antibacterianos/uso terapêutico , Comorbidade , Hospitalização/estatística & dados numéricos , Humanos , Internacionalidade , Estudos Prospectivos , Testes de Função Respiratória , Índice de Gravidade de Doença , Espanha/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Lung cancer screening (LCS) has the potential to reduce the risk of lung cancer death in healthy individuals, but the impact of coexisting chronic illnesses on LCS outcomes has not been well defined. Consideration of the complex relationship between baseline risk of lung cancer, treatment-related harms, and risk of death from competing causes is crucial in determining the balance of benefits and harms of LCS. OBJECTIVES: To summarize evidence, identify knowledge and research gaps, prioritize topics, and propose methods for future research on how best to incorporate comorbidities in making decisions regarding LCS. METHODS: A multidisciplinary group of international clinicians and researchers reviewed available data on the effects of comorbidities on LCS outcomes, focusing on the juxtaposition of lung cancer risk and competing risks of death, consideration of benefits and risks in patients with chronic obstructive pulmonary disease, communication of risk, and treatment of screen-detected lung cancer. RESULTS: This statement identifies gaps in knowledge regarding how comorbidities and competing causes of death impact outcomes in LCS, and we have developed questions to help guide future research efforts to better inform patient selection, education, and implementation of LCS. CONCLUSIONS: There is an urgent need for further research that can help guide clinical decision-making with patients who may not benefit from LCS owing to coexisting chronic illness. This statement establishes a research framework to address essential questions regarding how to incorporate and communicate risks of comorbidities into patient selection and decisions regarding LCS.
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Doença Crônica , Comorbidade , Detecção Precoce de Câncer/normas , Neoplasias Pulmonares/diagnóstico , Programas de Rastreamento/normas , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sociedades MédicasRESUMO
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is an independent risk factor for cardiovascular (CV) disease, one of the most frequent causes of death in COPD patients. The goal of the present study was to evaluate the prognostic value of non-invasive CV risk markers in COPD patients. METHODS: CV risk was prospectively evaluated in 287 COPD patients using non-invasive markers including the Framingham score, the Systematic Coronary Risk Evaluation (SCORE) charts, coronary arterial calcium (CAC), epicardial adipose tissue (EAT), as well as clinical, biochemical and physiological variables. The predictive power of each parameter was explored using CV events as the main outcome. RESULTS: During a median follow up of 65 months (ICR: 36-100), 44 CV events were recorded, 12 acute myocardial infarctions (27.3%), 10 ischemic heart disease/angina (22.7%), 12 peripheral artery disease events requiring surgery (27.3%) and 10 strokes (22.7%). A total of 35 CV deaths occurred during that period. Univariable analysis determined that age, hypertension, CRP, total Cholesterol, LDL-Cholesterol, Framingham score and CAC were independently associated with CV events. Multivariable analysis identified CAC as the best predictor of CV events (HR; 95%CI: 1.32; 1.19-1.46, p < 001). CONCLUSIONS: In COPD patients attending pulmonary clinics, CAC was the best independent non-invasive predictor of CV events. This tool may help evaluate the risk for a CV event in patients with COPD. Larger studies should reproduce and validate these findings.
Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fumar/sangue , Fumar/epidemiologia , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Fatores de Risco , Fumar/efeitos adversos , Espirometria/métodos , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico , Calcificação Vascular/epidemiologiaRESUMO
Lung cancer has been linked to the changes in lung function characteristic of chronic obstructive pulmonary disease (COPD) and to the changes in lung morphology seen in emphysema. It seems that a common thread of smoking-induced lung injury can be traced to all three diseases. However, the association is not as straightforward as it may seem; for example, even never-smokers with emphysema have an increased risk of lung cancer. Whether lung cancer, COPD, and emphysema are linked by common genes, mechanisms, causes, or a combination thereof, understanding the associations between them has become a priority for research regarding tobacco-related illnesses. A better delineation of the relationships between these three entities may lead to significant improvements in the effectiveness of lung cancer screening programs, and to reductions in the morbidity and mortality associated with these deadly diseases.
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Detecção Precoce de Câncer , Enfisema/complicações , Neoplasias Pulmonares/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapiaRESUMO
PURPOSE OF REVIEW: An important association has been described between chronic obstructive pulmonary disease (COPD) and lung cancer, where different mechanisms have been proposed. There is no unique cause for this association, as COPD is by itself a heterogeneous disease, in which their classical phenotypes (i.e., emphysema and chronic bronchitis) each play an important role in lung cancer development. We will discuss recent evidence that links these two diseases and specific characteristics found in lung cancers from patients with COPD. RECENT FINDINGS: Molecular studies have found specific gene expressions (reduction and overexpression) in lung tumors from patients with COPD, which likely predispose to increased methylation during lung carcinogenesis, and are associated with aggressiveness. Recent evidence suggests that lung cancer risk is higher in individuals with long telomeres, and that this effect takes place well in advance of diagnosis. Lung cancer is likely to develop in areas of the lung with greater emphysema and the severity of the latter is associated with larger and more aggressive tumors. SUMMARY: Clinical and molecular studies have found that lung cancers that develop in patients with COPD and/or emphysema appear to be more aggressive and have a distinct molecular profile when compared with tumors from patients without an underlying lung disease. This could have important implications when deciding on personalized treatments.
Assuntos
Neoplasias Pulmonares/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/fisiopatologia , Obstrução das Vias Respiratórias/complicações , Obstrução das Vias Respiratórias/fisiopatologia , Bronquite Crônica/complicações , Bronquite Crônica/fisiopatologia , Humanos , Pulmão/patologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/genética , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/genética , Enfisema Pulmonar/complicações , Enfisema Pulmonar/genética , Risco , Fumaça , Fumar/efeitos adversos , NicotianaRESUMO
RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) are at high risk for lung cancer (LC) and represent a potential target to improve the diagnostic yield of screening programs. OBJECTIVES: To develop a predictive score for LC risk for patients with COPD. METHODS: The Pamplona International Early Lung Cancer Detection Program (P-IELCAP) and the Pittsburgh Lung Screening Study (PLuSS) databases were analyzed. Only patients with COPD on spirometry were included. By logistic regression we determined which factors were independently associated with LC in PLuSS and developed a COPD LC screening score (COPD-LUCSS) to be validated in P-IELCAP. MEASUREMENTS AND MAIN RESULTS: By regression analysis, age greater than 60, body mass index less than 25 kg/m(2), pack-years history greater than 60, and emphysema presence were independently associated with LC diagnosis and integrated into the COPD-LUCSS, which ranges from 0 to 10 points. Two COPD-LUCSS risk categories were proposed: low risk (scores 0-6) and high risk (scores 7-10). In comparison with low-risk patients, in both cohorts LC risk increased 3.5-fold in the high-risk category. CONCLUSIONS: The COPD-LUCSS is a good predictor of LC risk in patients with COPD participating in LC screening programs. Validation in two different populations adds strength to the findings.
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Neoplasias Pulmonares/diagnóstico , Programas de Rastreamento/métodos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Adulto , Distribuição por Idade , Idoso , Detecção Precoce de Câncer , Europa (Continente) , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/mortalidade , Enfisema Pulmonar/diagnóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Distribuição por Sexo , Fumar/efeitos adversos , Espirometria , Inquéritos e Questionários , Estados UnidosRESUMO
RATIONALE: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55-74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity. OBJECTIVES: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion. METHODS: Participants from the Pamplona International Early Lung Action Detection Program (P-IELCAP; n = 3,061) and the Pittsburgh Lung Screening Study (PLuSS; n = 3,638) were considered. LC cumulative frequencies, incidence densities, and annual detection rates were calculated in three hypothetical cohorts, including subjects who met NLST criteria alone, those with computed tomography-detected emphysema, and those who met NLST criteria and/or had emphysema. MEASUREMENTS AND MAIN RESULTS: Thirty-six percent and 59% of P-IELCAP and PLuSS participants, respectively, met NLST criteria. Among these, higher LC incidence densities and detection rates were observed. However, applying NLST criteria to our original cohorts would miss as many as 39% of all LC. Annual screening of subjects meeting either NLST criteria or having emphysema detected most cancers (88% and 95% of incident LC of P-IELCAP and PLuSS, respectively) despite reducing the number of screened participants by as much as 52%. CONCLUSIONS: LC screening based solely on NLST criteria could miss a significant number of LC cases. Combining NLST criteria and emphysema to select screening candidates results in higher LC detection rates and a lower number of cancers missed.
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Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Programas de Rastreamento/métodos , Seleção de Pacientes , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/epidemiologia , Idoso , Comorbidade , Detecção Precoce de Câncer/métodos , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
Multimorbidity frequently affects the ageing population and their co-existence may not occur at random. Understanding their interactions and that with clinical variables could be important for disease screening and management.In a cohort of 1969 chronic obstructive pulmonary disease (COPD) patients and 316 non-COPD controls, we applied a network-based analysis to explore the associations between multiple comorbidities. Clinical characteristics (age, degree of obstruction, walking, dyspnoea, body mass index) and 79 comorbidities were identified and their interrelationships quantified. Using network visualisation software, we represented each clinical variable and comorbidity as a node with linkages representing statistically significant associations.The resulting COPD comorbidity network had 428, 357 or 265 linkages depending on the statistical threshold used (p≤0.01, p≤0.001 or p≤0.0001). There were more nodes and links in COPD compared with controls after adjusting for age, sex and number of subjects. In COPD, a subset of nodes had a larger number of linkages representing hubs. Four sub-networks or modules were identified using an inter-linkage affinity algorithm and their display provided meaningful interactions not discernible by univariate analysis.COPD patients are affected by larger number of multiple interlinked morbidities which clustering pattern may suggest common pathobiological processes or be utilised for screening and/or therapeutic interventions.
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Comorbidade , Serviços de Informação , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Distribuição por Idade , Idoso , Análise por Conglomerados , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Distribuição por Sexo , Estatística como Assunto , Análise de SobrevidaRESUMO
Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting.Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis.57 patients (34 treatment and 23 control) had efficacy results at 3â months; 34 (21 treatment and 13 control) at 6â months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6â months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalisation (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events.Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility.
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Adesivo Tecidual de Fibrina/uso terapêutico , Pneumonectomia/métodos , Enfisema Pulmonar/tratamento farmacológico , Enfisema Pulmonar/cirurgia , Qualidade de Vida , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/mortalidade , Testes de Função Respiratória , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
BACKGROUND: The Global Obstructive Lung Disease (GOLD) 2011 revision recommends the multidimensional assessment of COPD including comorbidities and has developed a disease categories system (ABCD) attempting to implement this strategy. The added value provided by quantifying comorbidities and integrating them to multidimensional indices has not been explored. OBJECTIVE: Compare the prognostic value of the GOLD ABCD categories versus the BMI, Obstruction, Dyspnea, Exercise (BODE) index, and explore the added prognostic value of comorbidities evaluation to this multidimensional assessment. METHODS: From the patients who have been enrolled in the BODE study, we selected the most recent ones who had the available information needed to classify them by the ABCD GOLD categories. Cox proportional hazards ratios for all-cause mortality were performed for GOLD categories and BODE index. The added value of the comorbidity Copd cO-morbidity TEst (COTE) index was also explored using receiver operating curves (ROC) values. RESULTS: 707 patients were followed for 50±30â months including all degrees of airway limitation and BODE index severity. ABCD GOLD predicted global mortality (HR: 1.47; 95% CI 1.28 to 1.70) as did the BODE index (HR: 2.02; 95% CI 1.76 to 2.31). Area under the curve (AUC) of ROC for ABCD GOLD was 0.68; (95% CI 0.64 to 0.73) while for the BODE index was 0.71 (95% CI 0.67 to 0.76). The C statistics value was significantly higher for the observed difference. Adding the COTE index to the BODE index improved its AUC to 0.81 (95% CI 0.77 to 0.85), (χ(2)=40.28, p<0.001). CONCLUSIONS: In this population of COPD patients, the BODE index had a better survival prediction than the ABCD GOLD categories. Adding the COTE to the BODE index was complimentary and significantly improved outcome prediction.
Assuntos
Doença Pulmonar Obstrutiva Crônica/classificação , Índice de Gravidade de Doença , Idoso , Área Sob a Curva , Comorbidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Curva ROCRESUMO
Chronic obstructive pulmonary disease (COPD), although frequent in older individuals, can also occur at younger age; this latter population has not been well described. We reviewed the functional progression of 1708 patients with COPD attending pulmonary clinics. Those with three or more annual spirometries were divided into those who, at enrolment, were ≤ 55 (n = 103) or ≥ 65 (n = 463) years of age (younger and older COPD, respectively). Baseline and annual changes in lung function (forced expiratory volume in 1 s (FEV1)) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) score were recorded and compared between both groups. Severity distribution by Global Initiative for Chronic Obstructive Lung Disease and BODE scores were similar in both groups, except for mild obstruction, which was higher in the younger group. Mean FEV1 decline was 38.8 and 40.6 mL · year(-1), while BODE scores increased 0.19 and 0.23 units per year, for younger and older COPD, respectively. Both groups had similar proportion of FEV1 rapid decliners (42% and 46%, respectively). The severity distribution and progression of disease in younger patients with COPD is similar to that of patients of older age. This observation suggests that younger individuals presenting with COPD develop the disease from an already compromised pulmonary and systemic status, complementing the model of steeper decline of lung function proposed by Fletcher and Peto.
Assuntos
Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/terapia , Idoso , Antropometria , Índice de Massa Corporal , Estudos de Coortes , Progressão da Doença , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Estudos Prospectivos , Pneumologia/normas , Testes de Função Respiratória , Índice de Gravidade de Doença , EspirometriaRESUMO
PURPOSE: The tumour molecular profile predicts the activity of epidermal growth factor receptor (EGFR) inhibitors in non-small-cell lung cancer (NSCLC). However, tissue availability and tumour heterogeneity limit its assessment. We evaluated whether [(18)F]FDG PET might help predict KRAS and EFGR mutation status in NSCLC. METHODS: Between January 2005 and October 2011, 340 NSCLC patients were tested for KRAS and EGFR mutation status. We identified patients with stage III and IV disease who had undergone [(18)F]FDG PET/CT scanning for initial staging. SUVpeak, SUVmax and SUVmean of the single hottest tumour lesions were calculated, and their association with KRAS and EGFR mutation status was assessed. A receiver operator characteristic (ROC) curve analysis and a multivariate analysis (including SUVmean, gender, age and AJCC stage) were performed to identify the potential value of [(18)F]FDG PET/CT for predicting KRAS mutation. RESULTS: From 102 patients staged using [(18)F]FDG PET/CT, 28 (27%) had KRAS mutation (KRAS+), 22 (22%) had EGFR mutation (EGFR+) and 52 (51%) had wild-type KRAS and EGFR profiles (WT). KRAS+ patients showed significantly higher [(18)F]FDG uptake than EGFR+ and WT patients (SUVmean 9.5, 5.7 and 6.6, respectively; p < 0.001). No significant differences were observed in [(18)F]FDG uptake between EGFR+ patients and WT patients. ROC curve analysis for KRAS mutation status discrimination yielded an area under the curve of 0.740 for SUVmean (p < 0.001). The multivariate analysis showed a sensitivity and specificity of 78.6% and 62.2%, respectively, and the AUC was 0.773. CONCLUSION: NSCLC patients with tumours harbouring KRAS mutations showed significantly higher [(18)F]FDG uptake than WT patients, as assessed in terms of SUVpeak, SUVmax and SUVmean. A multivariate model based on age, gender, AJCC stage and SUVmean might be used as a predictive marker of KRAS mutation status in patients with stage III or IV NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Receptores ErbB/genética , Fluordesoxiglucose F18 , Neoplasias Pulmonares/diagnóstico por imagem , Mutação , Tomografia por Emissão de Pósitrons , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Proto-Oncogênicas p21(ras) , Tomografia Computadorizada por Raios XRESUMO
Lung cancer screening using low-dose computed tomography (LDCT) carefully implemented has been found to reduce deaths from lung cancer. Optimal management starts with selection of eligibility criteria, counseling of screenees, smoking cessation, selection of the regimen of screening which specifies the imaging protocol, and workup of LDCT findings. Coordination of clinical, radiologic, and interventional teams and ultimately treatment of diagnosed lung cancers under screening determine the benefit of LDCT screening. Ethical considerations of who should be eligible for LDCT screening programs are important to provide the benefit to as many people at risk of lung cancer as possible. Unanticipated diseases identified on LDCT may offer important benefits through early detection of leading global causes of death, such as cardiovascular diseases and chronic obstructive pulmonary disease, as the latter may result from conditions such as emphysema and bronchiectasis, which can be identified early on LDCT. This report identifies the key components of the regimen of LDCT screening for lung cancer which include the need for a management system to provide data for continuous updating of the regimen and provides quality assurance assessment of actual screenings. Multidisciplinary clinical management is needed to maximize the benefit of early detection, diagnosis, and treatment of lung cancer. Different regimens have been evolving throughout the world as the resources and needs may be different, for countries with limited resources. Sharing of results, further knowledge, and incorporation of technologic advances will continue to accelerate worldwide improvements in the diagnostic and treatment approaches.