Characterization of Dyspnea in Veteran Lung Cancer Survivors Following Curative-Intent Therapy.

PurposeDyspnea is highly prevalent in lung cancer survivors following curative-intent therapy. We aimed to identify clinical predictors or determinants of dyspnea and characterize its relationship with functional exercise capacity (EC).MethodsIn an analysis of data from a cross-sectional study of lung cancer survivors at the VA San Diego Healthcare System who completed curative-intent therapy for stage I-IIIA disease ≥1 mo previously, we tested a thorough list of comorbidities, lung function, and lung cancer characteristics. We assessed dyspnea using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer Module 13 (LC13) and functional EC using the 6-minute walk. We replicated results with the University of California San Diego Shortness of Breath Questionnaire.ResultsIn 75 participants at a median of 12 mo since treatment completion, the mean ± SD LC13-Dyspnea score was 35.3 ± 26.2; 60% had abnormally high dyspnea. In multivariable linear regression analyses, significant clinical predictors or determinants of dyspnea were (β [95% CI]) psychiatric illness (-20.8 [-32.4 to -9.09]), heart failure with reduced ejection fraction (-15.5 [-28.0 to -2.97]), and forced expiratory volume in the first second of expiration (-0.28 [-0.49 to -0.06]). Dyspnea was an independent predictor of functional EC (-1.54 [-2.43 to -0.64]). These results were similar with the University of California San Diego Shortness of Breath Questionnaire.ConclusionWe identified clinical predictors or determinants of dyspnea that have pathophysiological bases. Dyspnea was independently associated with functional EC. These results have implications in efforts to reduce dyspnea and improve exercise behavior and functional EC in lung cancer survivors following curative-intent therapy

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Time to treatment and survival in veterans with lung cancer eligible for curative intent therapy.

BackgroundThe Institute of Medicine emphasizes care timeliness as an important quality metric. We assessed treatment timeliness in stage I-IIIA lung cancer patients deemed eligible for curative intent therapy and analyzed the relationship between time to treatment (TTT) and timely treatment (TT) with survival.MethodsWe retrospectively reviewed consecutive cases of stage I-IIIA lung cancer deemed eligible for curative intent therapy at the VA San Diego Healthcare System between 10/2010-4/2017. We defined TTT as days from chest tumor board to treatment initiation and TT using guideline recommendations. We used multivariable (MVA) Cox proportional hazards regressions for survival analyses.ResultsIn 177 veterans, the median TTT was 35 days (29 days for chemoradiation, 36 for surgical resection, 42 for definitive radiation). TT occurred in 33% or 77% of patients when the most or least timely guideline recommendation was used, respectively. Patient characteristics associated with longer TTT included other cancer history, high simplified comorbidity score, stage I disease, and definitive radiation treatment. In MVA, TTT and TT [HR 0.53 (95% CI 0.27, 1.01) for least timely definition] were not associated with OS in stage I-IIIA patients, or disease-free survival in subgroup analyses of 122 stage I patients [HR 1.49 (0.62, 3.59) for least timely definition].ConclusionTreatment was timely in 33-77% of veterans with lung cancer deemed eligible for curative intent therapy. TTT and TT were not associated with survival. The time interval between diagnosis and treatment may offer an opportunity to deliver or improve other cancer care

NSAIDs May Protect Against Age-Related Brain Atrophy

The use of non-steroidal anti-inflammatory drugs (NSAIDs) in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25) compared to non-user controls (n = 50). All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume

Classifying Chronic Lower Respiratory Disease Events in Epidemiologic Cohort Studies

Rationale: One in 12 adults has chronic obstructive pulmonary disease or asthma. Acute exacerbations of these chronic lower respiratory diseases (CLRDs) are a major cause of morbidity and mortality. Valid approaches to classifying cases and exacerbations in the general population are needed to facilitate prevention research

CSF T-Tau/Aβ42 Predicts White Matter Microstructure in Healthy Adults at Risk for Alzheimer’s Disease

Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ42 are linked with Alzheimer’s disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ42, total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ42 were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ42 levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter

Longitudinal change in the BODE index predicts mortality in severe emphysema

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91943/1/2008 AJRCCM Longitudinal change in the BODE index predicts mortality in severe emphysema.pd

Sex Differences in Severe Pulmonary Emphysema

Rationale: Limited data on sex differences in advanced COPD are available. Objectives: To compare male and female emphysema patients with severe disease. Methods: One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. Measurements and Main Results: Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower bodymass index (BMI), shorter smoking history, less severe airflow obstruction, lower DLCO and arterial PO2, higher arterial PCO2, shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV1% predicted, age, number of packyears, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. Conclusions: In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.The National Emphysema Treatment Trial (NETT) was supported by contracts with the National Heart, Lung, and Blood Institute (N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119); the Centers for Medicare and Medicaid Services (CMS; formerly the Health Care Financing Administration); and the Agency for Healthcare Research and Quality (AHRQ). J.L.C. is supported by funding from a Research Enhancement Award Program (REAP) from the Biomedical Laboratory Research & Development Service, Department of Veterans Affairs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91968/1/2007 Martinez AJRCCM Sex Differences in Empy.pd

Sleep-disordered Breathing in Hispanic/Latino Individuals of Diverse Backgrounds. The Hispanic Community Health Study/Study of Latinos

Rationale: Hispanic/Latino populations have a high prevalence of cardiovascular risk factors and may be at risk for sleep-disordered breathing (SDB). An understanding of SDB among these populations is needed given evidence that SDB increases cardiovascular risk