Lung function decline in relation to diagnostic criteria for airflow obstruction in respiratory symptomatic subjects

Contains fulltext : 108583.pdf (publisher's version ) (Open Access)BACKGROUND: Current COPD guidelines advocate a fixed < 0.70 FEV1/FVC cutpoint to define airflow obstruction. We compared rate of lung function decline in respiratory symptomatic 40+ subjects who were 'obstructive' or 'non-obstructive' according to the fixed and/or age and gender specific lower limit of normal (LLN) FEV1/FVC cutpoints. METHODS: We studied 3,324 respiratory symptomatic subjects referred to primary care diagnostic centres for spirometry. The cohort was subdivided into four categories based on presence or absence of obstruction according to the fixed and LLN FEV1/FVC cutpoints. Postbronchodilator FEV1 decline served as primary outcome to compare subjects between the respective categories. RESULTS: 918 subjects were obstructive according to the fixed FEV1/FVC cutpoint; 389 (42%) of them were non-obstructive according to the LLN cutpoint. In smokers, postbronchodilator FEV1 decline was 21 (SE 3) ml/year in those non-obstructive according to both cutpoints, 21 (7) ml/year in those obstructive according to the fixed but not according to the LLN cutpoint, and 50 (5) ml/year in those obstructive according to both cutpoints (p = 0.004). CONCLUSION: This study showed that respiratory symptomatic 40+ smokers and non-smokers who show FEV1/FVC values below the fixed 0.70 cutpoint but above their age/gender specific LLN value did not show accelerated FEV1 decline, in contrast with those showing FEV1/FVC values below their LLN cutpoint

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Measures of frailty in population-based studies: An overview

Although research productivity in the field of frailty has risen exponentially in recent years, there remains a lack of consensus regarding the measurement of this syndrome. This overview offers three services: first, we provide a comprehensive catalogue of current frailty measures; second, we evaluate their reliability and validity; third, we report on their popularity of use

Genetic contributions to variation in general cognitive function:a meta-analysis of genome-wide association studies in the CHARGE consortium (<i>N</i>=53 949)

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10−9, MIR2113; rs17522122, P=2.55 × 10−8, AKAP6; rs10119, P=5.67 × 10−9, APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10−6). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10−17). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer’s disease: TOMM40, APOE, ABCG1 and MEF2C

Asthma&ndash;COPD overlap syndrome in the US: a prospective population-based analysis of patient-reported outcomes and health care utilization

Carlos A Vaz Fragoso,1,2 Terrence E Murphy,1 George O Agogo,1 Heather G Allore,1,3 Gail J McAvay1 1Department of Medicine, Yale School of Medicine, New Haven, 2Veterans Affairs Clinical Epidemiology Research Center, West Haven, 3Department of Biostatistics, Yale School of Public Health, New Haven, CT, USA Background: Prior work suggests that asthma&ndash;COPD overlap syndrome (ACOS) has a greater health burden than asthma alone or COPD alone. In the current study, we have further evaluated the health burden of ACOS in a nationally representative sample of the US population, focusing on patient-reported outcomes and health care utilization and on comparisons with asthma alone and COPD alone. Patient-reported outcomes are especially meaningful, as these include functional activities that are highly valued by patients and are the basis for patient-centered care.Methods: Using data from the Medical Expenditure Panel Survey (MEPS), we evaluated patient-reported outcomes and health care utilization among participants who were aged 40&ndash;85 years and had self-reported, physician-diagnosed asthma or COPD. MEPS administered five rounds of interviews, at baseline and approximately every 6 months over 2.5 years. Patient-reported outcomes included activities of daily living (ADLs), mobility, social/recreational activities, disability days in bed, and health status (Short Form 12, Version 2). Health care utilization included outpatient and emergency department (ED) visits, and hospitalization.Results: Of 3,486 participants with asthma or COPD, 1,585 (45.4%) had asthma alone, 1,294 (37.1%) had COPD alone, and 607 (17.4%) had ACOS. Relative to asthma alone, ACOS was significantly associated with higher odds of prevalent disability in ADLs and limitations in mobility and social/recreational activities (adjusted odds ratios [adjORs]: 1.91&ndash;3.98), as well as with higher odds of incident limitations in mobility and social/recreational activities, disability days in bed, and respiratory-based outpatient and ED visits, and hospitalization (adjORs: 1.86&ndash;2.35). In addition, ACOS had significantly worse physical and mental health scores than asthma alone (P-values &lt;0.0001). Relative to COPD alone, ACOS was significantly associated with higher odds of prevalent limitations in mobility and social/recreational activities (adjORs: 1.68&ndash;2.06), as well as with higher odds of incident disability days in bed and respiratory-based outpatient and ED visits (adjORs: 1.48&ndash;1.74). In addition, ACOS had a significantly worse physical health score, but similar mental health score, as compared with COPD alone (P-values 0.0025 and 0.1578, respectively).Conclusion: In the US, ACOS is associated with a greater health burden, including patient-reported outcomes and health care utilization, relative to asthma alone and COPD alone. Keywords: disability, mobility, activities of daily living, social, recreationa

Respiratory impairment of older persons: when less means more

BACKGROUND: Among older persons, within the clinical context of respiratory symptoms and mobility, evidence suggests that improvements are warranted regarding the current approach for identifying respiratory impairment (i.e., a reduction in pulmonary function). METHODS: Among 3,583 white participants aged 65–80 (Cardiovascular Health Study), we calculated the prevalence of respiratory impairment using the current spirometric standard from the Global Initiative for Obstructive Lung Disease (GOLD) and an alternative spirometric approach termed Lambda-Mu-Sigma (LMS). Results for GOLD- and LMS-defined respiratory impairment were evaluated for their (cross-sectional) association with respiratory symptoms and gait speed, and also for the 5-year cumulative incidence probability of mobility disability. RESULTS: The prevalence of respiratory impairment was 49.7% (1,780/3,583) when using GOLD and 23.2% (831/3,583) when using LMS. Differences in prevalence were most evident among participants who had no respiratory symptoms, with respiratory impairment classified more often by GOLD (38.1% [326/855]) than LMS (12.3% [105/855]); as well as among participants who had normal gait speed, with respiratory impairment classified more often by GOLD (46.4% [1,003/2,164]) than LMS (19.3% [417/2,164]). Conversely, the 5-year cumulative incidence probability of mobility disability for respiratory impairment was higher for LMS than GOLD (0.313 and 0.249 for never-smokers, and 0.352 and 0.289 for ever-smokers, respectively), but was similar for normal spirometry by LMS or GOLD (0.193 and 0.185 for never-smokers, and 0.219 and 0.216 for ever-smokers, respectively). CONCLUSION: Among older persons, the LMS approach (versus the GOLD approach) classifies respiratory impairment less frequently in those who are asymptomatic, and is also more strongly associated with mobility disability

Phenotype of Normal Spirometry in an Aging Population

Rationale: In aging populations, the commonly used Global Initiative for Chronic Obstructive Lung Disease (GOLD) may misclassify normal spirometry as respiratory impairment (airflow obstruction and restrictive pattern), including the presumption of respiratory disease (chronic obstructive pulmonary disease [COPD]). Objectives: To evaluate the phenotype of normal spirometry as defined by a new approach from the Global Lung Initiative (GLI), overall and across GOLD spirometric categories. Methods: Using data from COPDGene (n = 10,131; ages 45–81; smoking history, ≥10 pack-years), we evaluated spirometry and multiple phenotypes, including dyspnea severity (Modified Medical Research Council grade 0–4), health-related quality of life (St. George’s Respiratory Questionnaire total score), 6-minute-walk distance, bronchodilator reversibility (FEV(1) % change), computed tomography–measured percentage of lung with emphysema (% emphysema) and gas trapping (% gas trapping), and small airway dimensions (square root of the wall area for a standardized airway with an internal perimeter of 10 mm). Measurements and Main Results: Among 5,100 participants with GLI-defined normal spirometry, GOLD identified respiratory impairment in 1,146 (22.5%), including a restrictive pattern in 464 (9.1%), mild COPD in 380 (7.5%), moderate COPD in 302 (5.9%), and severe COPD in none. Overall, the phenotype of GLI-defined normal spirometry included normal adjusted mean values for dyspnea grade (0.8), St. George’s Respiratory Questionnaire (15.9), 6-minute-walk distance (1,424 ft [434 m]), bronchodilator reversibility (2.7%), % emphysema (0.9%), % gas trapping (10.7%), and square root of the wall area for a standardized airway with an internal perimeter of 10 mm (3.65 mm); corresponding 95% confidence intervals were similarly normal. These phenotypes remained normal for GLI-defined normal spirometry across GOLD spirometric categories. Conclusions: GLI-defined normal spirometry, even when classified as respiratory impairment by GOLD, included adjusted mean values in the normal range for multiple phenotypes. These results suggest that among adults with GLI-defined normal spirometry, GOLD may misclassify normal phenotypes as having respiratory impairment