tbuckley/cabot-search huggingface dataset:
DNA hypermethylation within TERT promoter upregulates TERT expression in cancer
Authors: Donghyun D. Lee, Ricardo Leão, Martin Komosa, Marco Gallo, Cindy H. Zhang, Tatiana Lipman, Marc Remke, Abolfazl Heidari, Nuno Miguel Nunes, Joana D. Apolónio, Aryeh J. Price, Ramon Andrade De Mello, João S. Dias, David Huntsman, Thomas Hermanns, Peter J. Wild, Robert Vanner, Gelareh Zadeh, Jason Karamchandani, Sunit Das, Michael D. Taylor, Cynthia E. Hawkins, Jonathan D. Wasserman, Arnaldo Figueiredo, Robert J. Hamilton, Mark D. Minden, Khalida Wani, Bill Diplas, Hai Yan, Kenneth Aldape, Mohammad R. Akbari, Arnavaz Danesh, Trevor J. Pugh, Peter B. Dirks, Pedro Castelo-Branco, Uri Tabori
Journal: Journal of Clinical Investigation (2018)

Replicative immortality is a hallmark of cancer cells governed by telomere maintenance. Approximately 90% of human cancers maintain their telomeres by activating telomerase, driven by the transcriptional upregulation of telomerase reverse transcriptase (TERT). Although TERT promoter mutations (TPMs) are a major cancer-associated genetic mechanism of TERT upregulation, many cancers exhibit TERT upregulation without TPMs. In this study, we describe the TERT hypermethylated oncological region (THOR), a 433-bp genomic region encompassing 52 CpG sites located immediately upstream of the TERT core promoter, as a cancer-associated epigenetic mechanism of TERT upregulation. Unmethylated THOR repressed TERT promoter activity regardless of TPM status, and hypermethylation of THOR counteracted this repressive function. THOR methylation analysis in 1,352 human tumors revealed frequent (>45%) cancer-associated DNA hypermethylation in 9 of 11 (82%) tumor types screened. Additionally, THOR hypermethylation, either independently or along with TPMs, accounted for how approximately 90% of human cancers can aberrantly activate telomerase. Thus, we propose that THOR hypermethylation is a prevalent telomerase-activating mechanism in cancer that can act independently of or in conjunction with TPMs, further supporting the utility of THOR hypermethylation as a prognostic biomarker.
MA04.02 Responses and Durability in NSCLC Treated With Pegilodecakin and Anti-PD-1
Authors: E. Garon, D. Wong, J. Schneider, R. Aljumaily, W. Korn, J. Infante, M. Patel, K. Autio, K. Papadopoulos, A. Naing, N. Gabrail, P. Munster, J. Goldman, A. Hung, P. Van Vlasselaer, J. Leveque, M. Oft, D. Spigel
Journal: Journal of Thoracic Oncology (2018)
P1.01-11 Named Patient Use Program for Afatinib in Advanced NSCLC with Progression on Prior Therapy: Experience from Asian Centers
Authors: G. Chang, C.L. Lam, C. Tsai, Y. Chen, J. Shih, S. Aggarwal, S. Wang, S. Kim, Y. Kim, I. Wahid, R. Li, W. Lim, V. Sriuranpong, T.T. Chan, R. Lorence, P. Carriere, C. Raabe, A. Cseh, K. Park
Journal: Journal of Thoracic Oncology (2018)
P3.01-45 Multifactorial Gene Alterations in EGFR Bypass Pathway are Induced by Afatinib in T790M-Mutant NSCLC Resistant to Osmertinib
Authors: H. Ishii, K. Azuma, K. Sakai, Y. Naito, N. Matsuo, T. Tokito, K. Yamada, T. Hoshino, K. Nishio
Journal: Journal of Thoracic Oncology (2018)
Subgroup analysis of rucaparib in platinum-sensitive recurrent ovarian carcinoma: Effect of prior chemotherapy regimens in ARIEL3
Authors: D. Lorusso, R.L. Coleman, A.M. Oza, C. Aghajanian, A. Oaknin, A. Dean, N. Colombo, J.I. Weberpals, A.R. Clamp, G. Scambia, A. Leary, R.W. Holloway, M. Amenedo Gancedo, P.C. Fong, J.C. Goh, D.M. O’Malley, S. Banerjee, S. Goble, T. Cameron, J.A. Ledermann
Journal: Annals of Oncology (2018)
MA11.02 Increased CD3+ TIL Infiltration and Low FOXP3+/CD8+ TIL Ratio Can Predict Anti-PD-1 Therapeutic Response in Non-Small Cell Lung Cancer Patients
Authors: H. Kim, H.J. Kwon, Y.B. Han, S.Y. Park, E.S. Kim, J. Chung
Journal: Journal of Thoracic Oncology (2018)
Development of a pan-cancer biomarker panel for improved detection of MSI across all cancer types
Authors: J. Bacher, R. Halberg, P. Ward, E. Udho, K. Murphy, M. Uhr, L. Dubeau, J. Pettersson, D. Storts, S. Gallinger, D. Buchanan, M. Jenkins, N. Lindor, J. Eshleman
Journal: Annals of Oncology (2018)
Identification research and application for protein phosphorylation modification sites in human ovarian carcinoma
Authors: X. Zhan, N. Li
Journal: Annals of Oncology (2018)

Background: Phosphorylation modification, as one kind of protein post-translational modification (PTM), increases the diverse protein functions, such as cell signaling, protein folding, enzymatic activity, protein degradation, and their subcellular location. However, the subcellular phophoproteomic of ovarian carcinoma mitochondrial proteins has not been elucidated. Methods: Here, an 8-plex isobaric tag for relative and absolute quantification (iTRAQ) proteomics was used to identify mitochondrial expressed proteins (mtEPs) and phosphorylation modification sites of ovarian carcinomas relative to controls, followed by bioinformatics analysis. Results: The iTRAQ-based proteomics identified 5115 proteins and 99 phosphorylated proteins with quantitative information from purified mitochondrial samples, and 262 proteins were significantly related to overall survival in ovarian cancer patients. Interestingly, the results demonstrated that cancer cells exhibit an increased dependence on lipid metabolism, such as biosynthesis of unsaturated fatty acids, butanoate metabolism, fatty acid degradation, fatty acid metabolism, which might play an important role in ovarian carcinoma invasion and metastasis. Moreover 33 proteins related to lipid metabolism as potential markers for the development of ovarian carcinoma were identified.Additionally, 3 drug-associated phosphorylation proteins and 3 phosphorylation proteins as tumor markers in the plasma were obtained. The 99 phosphorylated proteins and TCGA data were integarated, thus obtained 9 important proteins. Among those, HSP60 were highly related with lipid metabolism. In cells with increased Hsp60 levels both the amounts of total mitochondrial short-chain acyl-CoA dehydrogenase (ACADS) proteins and folded ACADS were increased, which may influence mitochondrial protein folding and lipid metabolism. Conclusions: The current study provides a large-scale mitochondrial proteomic profiling and mitochondrion phosphoproteome with quantitative information, a certain number of proteins with the potential biomarkers, drug targets and a novel vision in the lipid metabolism bio-mechanism of human ovarian carcinoma. Legal entity responsible for the study: Hunan Engineering Laboratory for Structural Biology and Drug Design, Xiangya Hospital, Central South University. Funding: Xiangya Hospital Funds for Talent Introduction (to XZ), the grants from China "863" Plan Project (Grant No. 2014AA020610-1 to XZ), the National Natural Science Foundation of China (Grant No. 81272798 and 81572278 to XZ), and the Hunan Provincial Natural Science Foundation of China (Grant No. 14JJ7008 to XZ). Disclosure: All authors have declared no conflicts of interest.
P2.13-02 ALK-Translocation and Brain Metastases: A Retrospective Study. Correlation Between Clinical Outcome, Disease Burden and Management.
Authors: O. Grundberg, S. Friesland, S. Abdel-Halim, S. Gagatek, R. Karimi, A. Öjdahl-Boden, G. Tsakonas, M. Bradic-Lindh, K. Kölbeck, G. Wagenius, S. Ekman, K. Lindberg, L. De Petris
Journal: Journal of Thoracic Oncology (2018)
P1.05-10 Usefulness of Respiratory Dilatation Balloon in Tracheobronchial Stenosis Requiring Silicone Y-Stent Treatment
Authors: S. Mizuguchi, M. Takahama, R. Nakajima, H. Inoue, R. Ito, N. Nomura, R. Yamamoto
Journal: Journal of Thoracic Oncology (2018)
P3.01-75 RELAY+, an Exploratory Study of Gefitinib with Ramucirumab in Untreated Patients with EGFR Mutation-Positive Metastatic NSCLC
Authors: M. Nishio, K. Nishio, K. Suzukawa, Y. Omori, S. Enatsu, C. Visseren-Grul, K. Nakagawa
Journal: Journal of Thoracic Oncology (2018)
P3.01-55 SF2: A PCYT-2 Inhibitor Prototype is Capable of Inducing Citotoxicity in NSCLC
Authors: B. Kawamura, S. Teixeira, L. Mambelli, S. Jorge, M. Zaim, K. Pasqualoto, D. Levy, J. Barbuto, A. Ferreira
Journal: Journal of Thoracic Oncology (2018)
Use of lipegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia: Pan-European non-interventional study
Authors: G. Steger, P. Pichler, M. Airoldi, P. Mazza, C. Fontaine, J. Timmer Bonte, J.A. Walewski, J. Katolicka, M. Mikulova, M. Gasparic
Journal: Annals of Oncology (2018)
Olaparib plus paclitaxel sensitivity in biomarker subgroups of gastric cancer
Authors: Y.-Z. Liu, D. Hodgson, G. Locker, Z. Lai, D. Balcerzak, A. Sharpe, J.C. Barrett, M. Orr, T.S. Gutjahr, B. Dougherty, M.P. Roudier, X. Shi, R. Miller, W.H. Kim, X. Zeng, A. Ochiai, S.-A. Im, R.-H. Xu, N. Boku, Y.-J. Bang
Journal: Annals of Oncology (2018)
P1.01-72 FIND Trial: A Phase II Study to Evaluate the Efficacy of the FGFR-Inhibitor Erdafitinib in FGFR-Mutated and -Translocated Squamous NSCLC
Authors: L. Nogova, F. Malchers, G. Zadoyan, A. Hillmer, S. Merkelbach-Bruse, R. Riedel, S. Michels, B. Kharabi Masouleh, P. De Porre, A. Santiago-Walker, M. Scheffler, R. Fischer, D. Abdulla, R. Thomas, R. Büttner, J. Wolf
Journal: Journal of Thoracic Oncology (2018)
Effect of yoga on chemo-radiotherapy induced diabetes and hypertension (CRID-H) among cervical cancer patients at a regional cancer institute in south India
Authors: N.K. Nelson, I.A. Khaleel, M. ROY, H.B. Govardhan, N. Jasti, S. Suresh, R. Kashyap, L. Lokanath
Journal: Annals of Oncology (2018)
P1.16-15 Evaluation of Emphysema Severity by 3D-CT for Predicting Postoperative Respiratory Complications and Prognosis of Lung Cancer
Authors: Y. Makino, Y. Shimada, S. Maehara, J. Maeda, M. Kakihana, N. Kajiwara, T. Ohira, N. Ikeda
Journal: Journal of Thoracic Oncology (2018)
Bortezomib overcomes the negative impact of CXCR4 mutations on survival of Waldenstrom macroglobulinemia patients
Authors: Romanos Sklavenitis-Pistofidis, Marzia Capelletti, Chia-Jen Liu, Mairead Reidy, Oksana Zavidij, Daisy Huynh, Patrick Henrick, Alexandra Savell, Kaitlen Reyes, Bradley Rivotto, Mark Bustoros, Adriana Perilla-Glen, Lorenzo Trippa, Jorge J. Castillo, Steven P. Treon, Irene M. Ghobrial
Journal: Blood (2018)
Pre‐Emptive Transjugular Intrahepatic Portosystemic Shunt for Acute Variceal Bleed: Choose Your Patient Well!
Authors: Sandeep Satsangi
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. To the Editor: I read with great interest the manuscript published by Hernández‐Gea et al.1 The authors have eloquently demonstrated the survival benefit of pre‐emptive transjugular intrahepatic portosystemic shunt (p‐TIPS) placement in patients with Child C cirrhosis presenting with acute variceal bleed (AVB). I would like to emphasize on a critical aspect of this study: The authors conclude from the study that p‐TIPS should be the treatment of choice for patients with Child C cirrhosis presenting with AVB. It is imperative to note that the patients allotted to the p‐TIPS group in this study had a median model for end‐stage liver disease (MELD) score of around 15. The prognostic value of MELD score in predicting mortality after TIPS cannot be overemphasized. Casadaban et al.2 showed that survival rates after emergent TIPS placement for AVB were predicted by MELD scores, with a 90‐day mortality rate of 36% for MELD 19‐25 and 83% for MELD ≥26. As it is likely to have a patient with Child C cirrhosis (<14) to have a MELD score >18, it becomes extremely crucial to carefully delineate this subset of patients before recommending p‐TIPS as a treatment of choice in this group of patients. In a study by García‐Pagán et al.,3 early TIPS showed significant improvement in survival in patients with Child C cirrhosis presenting with AVB; however, the median MELD score of patients allotted to the early TIPS group was around 15, making it difficult to conclusively extrapolate this data to those with higher MELD scores. Ascha et al.4 conducted a retrospective analysis on a cohort of 144 patients with MELD score ≥15 who underwent TIPS procedure. The authors noted that in the first 2 months after TIPS, patients had a 56% higher risk of dying or requiring liver transplantation than matched non‐TIPS patients, which was statistically significant when corrected for Child score. This clearly highlights the importance of stratifying patients with Child C cirrhosis further based on their MELD score. Patients with Child C cirrhosis (<14) having a MELD score <18 should probably be offered p‐TIPS as the treatment of choice when presenting with AVB. However, more data is needed in those with a MELD score >18 to conclusively state the survival benefit of p‐TIPS in this subgroup of patients.
P1.01-23 High PD-L1 Expression is Less Common Than Expected Among Advanced NSCLC in Brazil. Are We Missing the Target?
Authors: A. Gelatti, V. Cordeiro De Lima, H. Freitas, G. Werutsky, A.M. Gaiger, C. Klock, P. Viola, C. Shiang, M. De Macedo, L. Lopes, F. Zaffaroni, L.H. Araujo, E. Mascarenhas, C. Mathias, F. Moura, G. Borges, C. Barrios, M. Zukin
Journal: Journal of Thoracic Oncology (2018)
Safety and efficacy of trifluridine/tipiracil (FTD/TPI) in metastatic colorectal cancer (mCRC) patients according to previous treatment with regorafenib in the international phase IIIb PRECONNECT study
Authors: J. Taieb, A. Falcone, S. Lonardi, T.J. Price, J.-B. Bachet, L. Wyrwicz, F. Ciardiello, M. Becquart, N. Mounedji, E. Van Cutsem
Journal: Annals of Oncology (2018)
The use of HPV16-E5, EGFR and pEGFR as prognostic biomarkers for oropharyngeal cancer patients
Authors: M. Taberna, M. Torres, M. Alejo, M. Mena, S. Tous, S. Marquez, M.A. Pavon, X. Leon, J. Garcia, M. Guix, R. Hijano, T. Bonfill, A. Aguilà, A. Lozano, R. Mesia Nin, L. Alemany, I.G. Bravo
Journal: Annals of Oncology (2018)
Phase II trial of perioperative PD-L1 inhibition with avelumab and mDCF chemotherapy for resectable locally advanced gastric and esophago-gastric adenocarcinoma
Authors: T. Alcindor, A. Awan, T. Opu, J. Asselah, M. Vanhuyse, C. Mueller, L. Ferri
Journal: Annals of Oncology (2018)
Updated safety and clinical activity results from a phase Ib study of atezolizumab + bevacizumab in hepatocellular carcinoma (HCC)
Authors: M.J. Pishvaian, M.S. Lee, B.-Y. Ryoo, S. Stein, K.-H. Lee, W. Verret, J. Spahn, H. Shao, B. Liu, K. Iizuka, C.-H. Hsu
Journal: Annals of Oncology (2018)
A phase Ia/IIb trial of the CXCR4 inhibitor X4P-001 and nivolumab for advanced renal cell carcinoma (RCC) that is unresponsive to nivolumab monotherapy
Authors: T.K. Choueiri, M.B. Atkins, T.L. Rose, R.S. Alter, E. Tsiroyannis, K. Niland, Y. Wang, S. Parasuraman, L. Gan, D.F. McDermott
Journal: Annals of Oncology (2018)
Abstract 15441: MURC/Cavin-4 Requires the Coiled-coil Domain for Membrane Trafficking of Caveolin-3 in Cardiomyocytes
Authors: Masahiro Nishi, Takehiro Ogata, Daisuke Naito, Tetsuro Hamaoka, Naohiko Nakanishi, Kotaro Miyagawa, Naoki Maruyama, Takeru Kasahara, Tomomi Ueyama
Journal: Circulation (2015)

[Background] Muscle-restricted coiled-coil protein (MURC), also referred to as Cavin-4, is a member of the cavin family that is cooperated with caveolins in caveola formation and function. Cavins are cytoplasmic proteins that have coiled-coil domains and form heteromeric complexes, which are recruited to caveolae in cells expressing caveolins. Among caveolins, caveolin-3 (Cav3) is exclusively expressed in muscle cells, similar to MURC/Cavin-4. In the heart, Cav3 overexpression contributes to cardiac protection, while its deficiency leads to progressive cardiomyopathy. Mutations in the MURC/Cavin-4 gene have been identified in patients with dilated cardiomyopathy. MURC/Cavin-4 has the coiled-coil domain; however, its functional significance remains unknown. [Methods and Results] MURC/Cavin-4 was localized at the plasma membrane in H9c2 cells, while a MURC/Cavin-4 mutant lacking the coiled-coil domain (ΔCC) was primarily localized to the cytoplasm. ΔCC bound to Cav3 and impaired membrane localization of Cav3 in cardiomyocytes. In addition, although ΔCC did not influence Cav3 mRNA expression, it decreased the Cav3 protein level in cardiomyocytes. MURC/Cavin-4 and ΔCC similarly induced cardiomyocytes hypertrophy; however, ΔCC showed higher hypertrophy-related fetal gene expression, such as ANP, BNP, and skeletal α-actin (SkA) mRNA expression and the βMHC/αMHC ratio, than MURC/Cavin-4. ΔCC induced ERK activation in cardiomyocytes. Cardiac function assessed by echocardiography was significantly impaired in transgenic mice expressing ΔCC in the heart (ΔCC-Tg mice) compared with non-transgenic (NTg) mice (% FS; 24.6 ± 2.4 % in ΔCC-Tg mice vs. 48.8 ± 2.5 % in NTg mice, p&lt;0.01), which was accompanied by cardiomyocyte hypertrophy, increased interstitial fibrosis, and the increase of lung weight-to-tibial-length ratio (LW/TL; 18.04 ± 2.41 in ΔCC-Tg mice vs. 7.51 ± 0.81 in NTg mice, p&lt;0.01). ΔCC-Tg hearts showed reduction of the Cav3 protein level and the activation of ERK. [Conclusions] These results reveal that MURC/Cavin-4 requires its coiled-coil domain to target the plasma membrane and Cav3 trafficking to the plasma membrane of cardiomyocytes, and that MURC/Cavin-4 functions as a crucial caveolar component to regulate cardiac function.
P2.16-01 Prognostic Significance of Preoperative Consolidation to Maximum Tumor Diameter Ratio and Suv-Max in Pathological Stage I Lung Adenocarcinoma
Authors: P. Akın Kabalak, Ü. Yılmaz, H. Ertürk, Ö. Özmen, Ş.M. Demiröz, D. Kızılgöz, S. Kavurgacı, T. Inal Cengiz
Journal: Journal of Thoracic Oncology (2018)
mFOLFOXIRI versus mFOLFOX6 as neoadjuvant chemotherapy in locally advanced rectal cancer: A propensity score analysis from two prospective trials
Authors: J. Zhang, Y. Deng, Z. Wu, H. Hu, Y. Cai, J. Ling
Journal: Annals of Oncology (2018)

Background: Neoadjuvant chemoradiotherapy (CRT) is the standard of treatment for locally advanced rectal cancer, but it delays administration of systemic chemotherapy, leading to high incidence of distant metastases. To enhance systemic chemotherapy and avoid the damage of radiation, full dose of neoadjuvant chemotherapy regimens with mFOLFOXIRI or mFOLFOX6 were both under investigation. Here, we aimed to compare the safety and efficacy of preoperative chemotherapy with mFOLFOXIRI versus mFOLFOX6 in locally advanced rectal cancer. Methods: Prospectively maintained databases of patients from two clinical trials (NCT01211210 and NCT02217020) underwent preoperative treatment for locally advanced rectal cancer in a single center were included. Those had received mFOLFOXIRI or mFOLFOX6 chemotherapy alone preoperatively was selected for this study, including 90 patients with mFOLFOXIRI and 119 patients with mFOLFOX6. All patients had undergone total mesorectal excision. A comparative analysis was performed after the implementation of propensity score matching on the 2 main cohorts (mFOLFOXIRI and mFOLFOX6). Results: A total of 209 patients were enrolled in the study. After propensity score matching, 180 patients were selected. 90 patients were comparable in the two groups. Higher pathologic complete response rate was observed in mFOLFOXIRI group than that of mFOLFOX6 group (16.7% vs. 5.6%, p = 0.03), although the tumor downstaging (ypT0-2N0M0) rate was comparable in this two group (41.1% vs. 37.8%, P = 0.76). The anal preservation rate was similar between the two groups (87.8% vs. 89.2%). Higher incidence of grade 3/4neutropenia (42.2% vs. 10%, P < 0.001) was shown in mFOLFOXIRI group than that of mFOLFOX6 group. Conclusions: Preoperative mFOLFOXIRI chemotherapy showed higher pCR rate than that of mFOLFOX6. The tumor downstaging rate was comparable between the two regimens. But the adverse events were more common in mFOLFOXIRI group. Whether the intensive regimen would improve the survival is unknown. Further follow-up is needed. Clinical trial identification: NCT01211210 and NCT02217020. Legal entity responsible for the study: Yanhong Deng. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Morphologic response to chemotherapy containing bevacizumab in patients with colorectal liver metastases (CLM): A post hoc analysis of the WJOG4407G phase III study
Authors: A. Hosokawa, K. Yamazaki, C. Matsuda, S. Ueda, H. Fujii, E. Baba, S. Okamura, M. Tsuda, T. Tamura, K. Shinozaki, T. Tsushima, T. Tsuda, T. Shirakawa, H. Yamashita, S. Morita, K. Muro
Journal: Annals of Oncology (2018)
PRISM: A randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma
Authors: F. Collinson, S. Brown, H. Buckley, G. Ainsworth, H. Howard, H. Poad, G. Carr, R.E. Banks, J. Brown, G. Velikova, J. Larkin, P. Nathan, T.B. Powles, N.S. Vasudev
Journal: Annals of Oncology (2018)
ERS technical standard on bronchial challenge testing: pathophysiology and methodology of indirect airway challenge testing
Authors: Teal S. Hallstrand, Joerg D. Leuppi, Guy Joos, Graham L. Hall, Kai-Håkon Carlsen, David A. Kaminsky, Allan L. Coates, Donald W. Cockcroft, Bruce H. Culver, Zuzana Diamant, Gail M. Gauvreau, Ildiko Horvath, Frans H.C. de Jongh, Beth L. Laube, Peter J. Sterk, Jack Wanger
Journal: European Respiratory Journal (2018)

Recently, this international task force reported the general considerations for bronchial challenge testing and the performance of the methacholine challenge test, a "direct" airway challenge test. Here, the task force provides an updated description of the pathophysiology and the methods to conduct indirect challenge tests. Because indirect challenge tests trigger airway narrowing through the activation of endogenous pathways that are involved in asthma, indirect challenge tests tend to be specific for asthma and reveal much about the biology of asthma, but may be less sensitive than direct tests for the detection of airway hyperresponsiveness. We provide recommendations for the conduct and interpretation of hyperpnoea challenge tests such as dry air exercise challenge and eucapnic voluntary hyperpnoea that provide a single strong stimulus for airway narrowing. This technical standard expands the recommendations to additional indirect tests such as hypertonic saline, mannitol and adenosine challenge that are incremental tests, but still retain characteristics of other indirect challenges. Assessment of airway hyperresponsiveness, with direct and indirect tests, are valuable tools to understand and to monitor airway function and to characterise the underlying asthma phenotype to guide therapy. The tests should be interpreted within the context of the clinical features of asthma.