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Obesity's effect on asthma extends to diagnostic criteria.

ABSTRACT: BACKGROUND:The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown. OBJECTIVES:We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects. METHODS:We performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE levels, blood eosinophil counts, and fraction of exhaled nitric oxide values in relationship to sputum eosinophil counts (>2%), as well as to determine whether cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the 3 weight groups. RESULTS:Overall, statistically significant but relatively weak correlations were observed among all 4 markers of inflammation. Within obese subjects, the only significant correlation found was between IgE levels and blood eosinophil counts (r = 0.33, P < .001); furthermore, all other correlations between inflammatory markers were approximately 0, including correlations with sputum eosinophil counts. In addition, the predictive value of each biomarker alone or in combination was poor in obese subjects. In fact, in obese subjects none of the biomarkers of inflammation significantly predicted the presence of high sputum eosinophil counts. Obese asthmatic subjects have lower cut points for IgE levels (268 IU), fraction of exhaled nitric oxide values (14.5 ppb), and blood eosinophil counts (96 cells/?L) than all other groups. CONCLUSIONS:In obese asthmatic subjects conventional biomarkers of inflammation are poorly predictive of eosinophilic airway inflammation. As such, biomarkers currently used to delineate eosinophilic inflammation in asthmatic subjects should be approached with caution in these subjects.

SUBMITTER: Lugogo N

PROVIDER: S-EPMC6076889 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Obesity's effect on asthma extends to diagnostic criteria.

Lugogo Njira N Green Cynthia L CL Agada Noah N Zhang Siyi S Meghdadpour Susanne S Zhou Run R Yang Siyun S Anstrom Kevin J KJ Israel Elliot E Martin Richard R Lemanske Robert F RF Boushey Homer H Lazarus Stephen C SC Wasserman Stephen I SI Castro Mario M Calhoun William W Peters Stephen P SP DiMango Emily E Chinchilli Vernon V Kunselman Susan S King Tonya S TS Icitovic Nikolina N Kraft Monica M

The Journal of allergy and clinical immunology 20170615 3

<h4>Background</h4>The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown.<h4>Objectives</h4>We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects.<h4>Methods</h4>We performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear corre ...[more]

PMID: 28624608

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Project description:BackgroundAsthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a condition characterized by the overlapping clinical features of asthma and COPD. To evaluate the appropriateness of different sets of ACO definition, we compared the clinical characteristics of the previously defined diagnostic criteria and the specialist opinion in this study.MethodsPatients enrolled in the KOrea COpd Subgroup Study (KOCOSS) were evaluated. Based on the questionnaire data, the patients were categorized into the ACO and non-ACO COPD groups according to the four sets of the diagnostic criteria.ResultsIn total 1,475 patients evaluated: 202 of 1,475 (13.6%), 32 of 1,475 (2.2%), 178 of 1,113 (16.0%), and 305 of 1,250 (24.4%) were categorized as ACO according to the modified Spanish Society of Pneumonology and Thoracic Surgery (SEPAR), American Thoracic Society (ATS) Roundtable, Global Initiative for Asthma (GINA)/Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, and the specialists diagnosis, respectively. The ACO group defined according to the GINA/GOLD criteria showed significantly higher St. George's Respiratory Questionnaire and COPD Assessment Test scores than the non-ACO COPD group. When the modified SEPAR definition was applied, the ACO group showed a significantly larger decrease in the forced expiratory volume in 1 second (FEV1, %). The ACO group defined by the ATS Roundtable showed significantly larger decrease in the forced vital capacity values compared to the non-ACO COPD group (-18.9% vs. -2.2%, p=0.007 and -412 mL vs. -17 mL, p=0.036). The ACO group diagnosed by the specialists showed a significantly larger decrease in the FEV1 (%) compared to the non-ACO group (-5.4% vs. -0.2%, p=0.003).ConclusionIn this study, the prevalence and clinical characteristics of ACO varied depending on the diagnostic criteria applied. With the criteria which are relatively easy to use, defining ACO by the specialists diagnosis may be more practical in clinical applications.

Project description:The radiologically isolated syndrome (RIS) was defined in 2009 as the presence of asymptomatic, incidentally identified demyelinating-appearing white matter lesions in the CNS within individuals lacking symptoms typical of multiple sclerosis (MS). The RIS criteria have been validated and predict the transition to symptomatic MS reliably. The performance of RIS criteria that require fewer MRI lesions is unknown. 2009-RIS subjects, by definition, fulfil three to four of four criteria for 2005 dissemination in space (DIS) and subjects fulfilling only one or two lesions in at least one 2017 DIS location were identified within 37 prospective databases. Univariate and multivariate Cox regression models were used to identify predictors of a first clinical event. Performances of different groups were calculated. Seven hundred and forty-seven subjects (72.2% female, mean age 37.7 ± 12.3 years at the index MRI) were included. The mean clinical follow-up time was 46.8 ± 45.4 months. All subjects had focal T2 hyperintensities suggestive of inflammatory demyelination on MRI; 251 (33.6%) fulfilled one or two 2017 DIS criteria (designated as Groups 1 and 2, respectively), and 496 (66.4%) fulfilled three or four 2005 DIS criteria representing 2009-RIS subjects. Group 1 and 2 subjects were younger than the 2009-RIS group and were more likely to develop new T2 lesions over time (P < 0.001). Groups 1 and 2 were similar regarding survival distribution and risk factors for transition to MS. At 5 years, the cumulative probability for a clinical event was 29.0% for Groups 1 and 2 compared to 38.7% for 2009-RIS (P = 0.0241). The presence of spinal cord lesions on the index scan and CSF-restricted oligoclonal bands in Groups 1-2 increased the risk of symptomatic MS evolution at 5 years to 38%, comparable to the risk of development in the 2009-RIS group. The presence of new T2 or gadolinium-enhancing lesions on follow-up scans independently increased the risk of presenting with a clinical event (P < 0.001). The 2009-RIS subjects or Groups 1 and 2 with at least two of the risk factors for a clinical event demonstrated better sensitivity (86.0%), negative predictive value (73.1%), accuracy (59.8%) and area under the curve (60.7%) compared to other criteria studied. This large prospective cohort brings Class I evidence that subjects with fewer lesions than required in the 2009 RIS criteria evolve directly to a first clinical event at a similar rate when additional risk factors are present. Our results provide a rationale for revisions to existing RIS diagnostic criteria.

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Project description:To develop criteria to identify thresholds for the minimally acceptable performance of physicians interpreting diagnostic mammography studies.In an institutional review board-approved HIPAA-compliant study, an Angoff approach was used to set criteria for identifying minimally acceptable interpretive performance for both workup after abnormal screening examinations and workup of a breast lump. Normative data from the Breast Cancer Surveillance Consortium (BCSC) was used to help the expert radiologist identify the impact of cut points. Simulations, also using data from the BCSC, were used to estimate the expected clinical impact from the recommended performance thresholds.Final cut points for workup of abnormal screening examinations were as follows: sensitivity, less than 80%; specificity, less than 80% or greater than 95%; abnormal interpretation rate, less than 8% or greater than 25%; positive predictive value (PPV) of biopsy recommendation (PPV2), less than 15% or greater than 40%; PPV of biopsy performed (PPV3), less than 20% or greater than 45%; and cancer diagnosis rate, less than 20 per 1000 interpretations. Final cut points for workup of a breast lump were as follows: sensitivity, less than 85%; specificity, less than 83% or greater than 95%; abnormal interpretation rate, less than 10% or greater than 25%; PPV2, less than 25% or greater than 50%; PPV3, less than 30% or greater than 55%; and cancer diagnosis rate, less than 40 per 1000 interpretations. If underperforming physicians moved into the acceptable range after remedial training, the expected result would be (a) diagnosis of an additional 86 cancers per 100,000 women undergoing workup after screening examinations, with a reduction in the number of false-positive examinations by 1067 per 100,000 women undergoing this workup, and (b) diagnosis of an additional 335 cancers per 100,000 women undergoing workup of a breast lump, with a reduction in the number of false-positive examinations by 634 per 100,000 women undergoing this workup.Interpreting physicians who fall outside one or more of the identified cut points should be reviewed in the context of an overall assessment of all their performance measures and their specific practice setting to determine if remedial training is indicated.

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Obesity's effect on asthma extends to diagnostic criteria.

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Obesity's effect on asthma extends to diagnostic criteria.

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