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Novel immunologic classification of aspergillosis in adult cystic fibrosis
Caroline G. Baxter, PhD, Graham Dunn, PhD, Andrew M. Jones, MD, Kevin Webb, MD, Robin Gore, PhD, Malcolm D. Richardson, PhD, David W. Denning, MD Journal of Allergy and Clinical Immunology Volume 132, Issue 3, Pages e10 (September 2013) DOI: /j.jaci Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 1 Boxplot distributions of immunologic, RT-PCR, and GM levels by latent class in 130 triazole-naive adult patients with CF. Journal of Allergy and Clinical Immunology , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig 2 ROC-curve analysis separating classes 2 + 4 from classes 1 + 3. ROC curve showing the performance of GM (optical index >0.5), sIgG (cutoff >75 mg/L) and real-time Aspergillus RT-PCR (Ct cutoff <34.5) for distinguishing both class 2 (ABPA) and class 4 (Aspergillus bronchitis) from classes 1 and 3. ROC, Receiver operating characteristic. Journal of Allergy and Clinical Immunology , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig E1 ROC-curve analysis of sIgE and tIgE performance in class separation. A, ROC-curve analysis of sIgE (AUC 0.99) and tIgE (AUC 0.96) separating class 2 (ABPA-S) plus class 3 (sensitized) from class 1 (nondisease) plus class 4 (Aspergillus bronchitis). B, ROC-curve analysis of sIgE (AUC 0.98) and tIgE (AUC 0.97) separating class 2 (ABPA-S) from all other classes. Classes 2 (ABPA-S) and 3 (sensitized) are separated from each other by using tIgE (AUC, 0.91) and sIgE (AUC, 0.90); tIgE > 400 kUI/L 78% sensitivity, 95% specificity; sIgE > 8.5 kUA/L 78% sensitivity, 79% specificity. Applying consensus criteria to class 2 (ABPA-S) shows that a value of >500 kUI/L (minimum diagnostic criteria for ABPA) separates class 2 from all other classes with a sensitivity of 70% and a specificity of 99%, whereas a level of >1000 kUI/L (classic ABPA) gives a sensitivity of 39% and a specificity of 100%. ROC-curve analysis shows that the optimum level is >185 kUI/L, giving 91% sensitivity and 90% specificity (AUC 0.97). AUC, Area under the curve; ROC, receiver operating characteristic; tIgE, total IgE. Journal of Allergy and Clinical Immunology , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig E2 Canonical discriminant functions. cdf1 and 2 are calculated for each patient and then represented by a dot on the graph. Each dot is labeled by the latent class they were originally assigned to. cdf1, Canonical discriminant function 1; cdf2, canonical discriminant function 2. Journal of Allergy and Clinical Immunology , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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Fig E3 Diagnostic algorithm to predict class membership for future patients. On comparison of this algorithm to the original latent class membership, using the 130 patients not on triazoles, 4 class 1 patients would be misclassified, 2 into class 3 and 2 into class 4. One patient would move from class 2 to class 3, giving an overall estimated error rate of The effect of dropping variables from the diagnostic rule, using linear discriminant analysis, is as follows: Drop RT-PCR, introduction of small error rate in class 3 but overall 5 patients still misclassified and error rate increases to Drop tIgE, introduction of error in class 3, 6 patients misclassified, and error rate increases to Drop sIgG, increased error rate in class 1, 6 patients misclassified, and error rate increases to Drop GM, error in all classes, 13 patients misclassified, and error rate increases to Drop sIgE, error in all classes, 19 patients misclassified, and error rate increases to tIgE, Total IgE. Journal of Allergy and Clinical Immunology , e10DOI: ( /j.jaci ) Copyright © 2013 American Academy of Allergy, Asthma & Immunology Terms and Conditions
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