Automation of the tax practice of the \u2790s;

https://egrove.olemiss.edu/aicpa_guides/1022/thumbnail.jp

Role of CED-4 in the activation of CED-3

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62523/1/388728a0.pd

Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function

Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms

Imaging-based clusters in current smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS)

Background Classification of COPD is usually based on the severity of airflow, which may not sensitively differentiate subpopulations. Using a multiscale imaging-based cluster analysis (MICA), we aim to identify subpopulations for current smokers with COPD. Methods Among the SPIROMICS subjects, we analyzed computed tomography images at total lung capacity (TLC) and residual volume (RV) of 284 current smokers. Functional variables were derived from registration of TLC and RV images, e.g. functional small airways disease (fSAD%). Structural variables were assessed at TLC images, e.g. emphysema and airway wall thickness and diameter. We employed an unsupervised method for clustering. Results Four clusters were identified. Cluster 1 had relatively normal airway structures; Cluster 2 had an increase of fSAD% and wall thickness; Cluster 3 exhibited a further increase of fSAD% but a decrease of wall thickness and airway diameter; Cluster 4 had a significant increase of fSAD% and emphysema. Clinically, Cluster 1 showed normal FEV1/FVC and low exacerbations. Cluster 4 showed relatively low FEV1/FVC and high exacerbations. While Cluster 2 and Cluster 3 showed similar exacerbations, Cluster 2 had the highest BMI among all clusters. Conclusions Association of imaging-based clusters with existing clinical metrics suggests the sensitivity of MICA in differentiating subpopulations

Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts

Rationale: Chronic obstructive pulmonary disease exacerbations are associated with disease progression, higher healthcare cost, and increased mortality. Published predictors of future exacerbations include previous exacerbation, airflow obstruction, poor overall health, home oxygen use, and gastroesophageal reflux

Airway Mucin Concentration as a Marker of Chronic Bronchitis

Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on the airway surfaces is hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation of transport in persons with muco-obstructive lung diseases. Under this model, it is postulated that a high mucin concentration produces the sputum and disease progression that are characteristic of chronic bronchitis

Variability in objective and subjective measures affects baseline values in studies of patients with COPD

Rationale: Understanding the reliability and repeatability of clinical measurements used in the diagnosis, treatment and monitoring of disease progression is of critical importance across all disciplines of clinical practice and in clinical trials to assess therapeutic efficacy and safety. Objectives: Our goal is to understand normal variability for assessing true changes in health status and to more accurately utilize this data to differentiate disease characteristics and outcomes. Methods: Our study is the first study designed entirely to establish the repeatability of a large number of instruments utilized for the clinical assessment of COPD in the same subjects over the same period. We utilized SPIROMICS participants (n = 98) that returned to their clinical center within 6 weeks of their baseline visit to repeat complete baseline assessments. Demographics, spirometry, questionnaires, complete blood cell counts (CBC), medical history, and emphysema status by computerized tomography (CT) imaging were obtained. Results: Pulmonary function tests (PFTs) were highly repeatable (ICC’s >0.9) but the 6 minute walk (6MW) was less so (ICC = 0.79). Among questionnaires, the Saint George’s Respiratory Questionnaire (SGRQ) was most repeatable. Self-reported clinical features, such as exacerbation history, and features of chronic bronchitis, often produced kappa values <0.6. Reported age at starting smoking and average number of cigarettes smoked were modestly repeatable (kappa = 0.76 and 0.79). Complete blood counts (CBC) variables produced intraclass correlation coefficients (ICC) values between 0.6 and 0.8. Conclusions: PFTs were highly repeatable, while subjective measures and subject recall were more variable. Analyses using features with poor repeatability could lead to misclassification and outcome errors. Hence, care should be taken when interpreting change in clinical features based on measures with low repeatability. Efforts to improve repeatability of key clinical features such as exacerbation history and chronic bronchitis are warranted

Imaging-based clusters in former smokers of the COPD cohort associate with clinical characteristics: the SubPopulations and intermediate outcome measures in COPD study (SPIROMICS)

Background: Quantitative computed tomographic (QCT) imaging-based metrics enable to quantify smoking induced disease alterations and to identify imaging-based clusters for current smokers. We aimed to derive clinically meaningful sub-groups of former smokers using dimensional reduction and clustering methods to develop a new way of COPD phenotyping. Methods: An imaging-based cluster analysis was performed for 406 former smokers with a comprehensive set of imaging metrics including 75 imaging-based metrics. They consisted of structural and functional variables at 10 segmental and 5 lobar locations. The structural variables included lung shape, branching angle, airway-circularity, airway-wall-thickness, airway diameter; the functional variables included regional ventilation, emphysema percentage, functional small airway disease percentage, Jacobian (volume change), anisotropic deformation index (directional preference in volume change), and tissue fractions at inspiration and expiration. Results: We derived four distinct imaging-based clusters as possible phenotypes with the sizes of 100, 80, 141, and 85, respectively. Cluster 1 subjects were asymptomatic and showed relatively normal airway structure and lung function except airway wall thickening and moderate emphysema. Cluster 2 subjects populated with obese females showed an increase of tissue fraction at inspiration, minimal emphysema, and the lowest progression rate of emphysema. Cluster 3 subjects populated with older males showed small airway narrowing and a decreased tissue fraction at expiration, both indicating air-trapping. Cluster 4 subjects populated with lean males were likely to be severe COPD subjects showing the highest progression rate of emphysema. Conclusions: QCT imaging-based metrics for former smokers allow for the derivation of statistically stable clusters associated with unique clinical characteristics. This approach helps better categorization of COPD sub-populations; suggesting possible quantitative structural and functional phenotypes.NIH [U01-HL114494, R01-HL112986, S10-RR022421]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2017R1D1A1B03034157]; Korea Ministry of Environment (MOE) [RE201806039]; NIH/NHLBI [HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Respiratory Symptoms Items from the COPD Assessment Test Identify Ever-Smokers with Preserved Lung Function at Higher Risk for Poor Respiratory Outcomes

Rationale: Ever-smokers without airflow obstruction scores greater than or equal to 10 on the COPD Assessment Test (CAT) still have frequent acute respiratory disease events (exacerbation-like), impaired exercise capacity, and imaging abnormalities. Identification of these subjects could provide new opportunities for targeted interventions. Objectives: We hypothesized that the four respiratory-related items of the CAT might be useful for identifying such individuals, with discriminative ability similar to CAT, which is an eight-item questionnaire used to assess chronic obstructive pulmonary disease impact, including nonrespiratory questions, with scores ranging from 0 to 40. Methods: We evaluated ever-smoker participants in the Subpopulations and Intermediate Outcomes in COPD Study without airflow obstruction (FEV1/FVC≥0.70; FVC above the lower limit of normal). Using the area under the receiver operating characteristic curve, we compared responses to both CAT and the respiratory symptom–related CAT items (cough, phlegm, chest tightness, and breathlessness) and their associations with longitudinal exacerbations. We tested agreement between the two strategies (k statistic), and we compared demographics, lung function, and symptoms among subjects identified as having high symptoms by each strategy. Results: Among 880 ever-smokers with normal lung function (mean age, 61 yr; 52% women) and using a CAT cutpoint greater than or equal to 10, we classified 51.8% of individuals as having high symptoms, 15.3% of whom experienced at least one exacerbation during 1-year follow-up. After testing sensitivity and specificity of different scores for the first four questions to predict any 1-year followup exacerbation, we selected cutpoints of 0–6 as representing a low burden of symptoms versus scores of 7 or higher as representing a high burden of symptoms for all subsequent comparisons. The four respiratory-related items with cutpoint greater than or equal to 7 selected 45.8% participants, 15.6% of whom experienced at least one exacerbation during follow-up. The two strategies largely identified the same individuals (agreement, 88.5%; k = 0.77; P \u3c 0.001), and the proportions of high-symptoms subjects who had severe dyspnea were similar between CAT and the first four CAT questions (25.9% and 26.8%, respectively), as were the proportions reporting impaired quality of life (66.9% and 70.5%, respectively) and short walking distance (22.4% and 23.1%, respectively). There was no difference in area under the receiver operating characteristic curve to predict 1-year follow-up exacerbations (CAT score ≥10, 0.66; vs. four respiratory items from CAT ≥ 7 score, 0.65; P = 0.69). Subjects identified by either method also hadmore depression/anxiety symptoms, poor sleep quality, and greater fatigue. Conclusions: Four CAT items on respiratory symptoms identified high-risk symptomatic ever-smokers with preserved spirometry as well as the CAT did. These data suggest that simpler strategies can be developed to identify these high-risk individuals in primary care