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3. Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma

Author

Dolgalev, Igor, Zhou, Hua, Murrell, Nina, Le, Hortense, Sakellaropoulos, Theodore, Coudray, Nicolas, Zhu, Kelsey, Vasudevaraja, Varshini, Yeaton, Anna, Goparaju, Chandra, Li, Yonghua, Sulaiman, Imran, Tsay, Jun-Chieh J., Meyn, Peter, Mohamed, Hussein, Sydney, Iris, Shiomi, Tomoe, Ramaswami, Sitharam, Narula, Navneet, Kulicke, Ruth, Davis, Fred P., Stransky, Nicolas, Smolen, Gromoslaw A., Cheng, Wei-Yi, Cai, James, Punekar, Salman, Velcheti, Vamsidhar, Sterman, Daniel H., Poirier, J. T., Neel, Ben, Wong, Kwok-Kin, Chiriboga, Luis, Heguy, Adriana, Papagiannakopoulos, Thales, Nadorp, Bettina, Snuderl, Matija, Segal, Leopoldo N., Moreira, Andre L., Pass, Harvey I., and Tsirigos, Aristotelis

Published
2023
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4. Pleural fluid microbiota as a biomarker for malignancy and prognosis

Author

Kwok, Benjamin, Wu, Benjamin G., Kocak, Ibrahim F., Sulaiman, Imran, Schluger, Rosemary, Li, Yonghua, Anwer, Raheel, Goparaju, Chandra, Ryan, Daniel J., Sagatelian, Marla, Dreier, Matthew S., Murthy, Vivek, Rafeq, Samaan, Michaud, Gaetane C., Sterman, Daniel H., Bessich, Jamie L., Pass, Harvey I., Segal, Leopoldo N., and Tsay, Jun-Chieh J.

Published
2023
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5. Pathomic Features Reveal Immune and Molecular Evolution From Lung Preneoplasia to Invasive Adenocarcinoma

Author

Chen, Pingjun, Rojas, Frank R., Hu, Xin, Serrano, Alejandra, Zhu, Bo, Chen, Hong, Hong, Lingzhi, Bandyoyadhyay, Rukhmini, Aminu, Muhammad, Kalhor, Neda, Lee, J. Jack, El Hussein, Siba, Khoury, Joseph D., Pass, Harvey I., Moreira, Andre L., Velcheti, Vamsidhar, Sterman, Daniel H., Fukuoka, Junya, Tabata, Kazuhiro, Su, Dan, Ying, Lisha, Gibbons, Don L., Heymach, John V., Wistuba, Ignacio I., Fujimoto, Junya, Solis Soto, Luisa M., Zhang, Jianjun, and Wu, Jia

Published
2023
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6. Asbestosis

Author

Henderson, Ian, primary, Sterman, Daniel H., additional, Smith, Robert L., additional, and Rom, William N., additional

Published
2022
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10. IMPACTS ON MANAGEMENT OF HIGH-RISK LUNG NODULES AND PATIENT OUTCOMES AFTER VIRTUAL REVIEW BY A MULTIDISCIPLINARY LUNG NODULE REVIEW BOARD

Author

MANGALICK, KESHAV, primary, REMAR, HUGH J, additional, NELSON, RACHEL, additional, BANVARD, MARIA, additional, ALISA BRAITHWAITE, KAREN, additional, MORGAN, MELISSA A, additional, BELL, JAIMIE, additional, LU, ANNIE D., additional, HASELTINE, MEGAN, additional, LI, WENYUAN, additional, SHUM, ELAINE, additional, BESSICH, JAMIE L, additional, GERACI, TRAVIS C, additional, AGARWALA, PRIYA, additional, MERCADO, JORGE M, additional, KENT, AMIE, additional, PASS, HARVEY I, additional, SCHNEIDER, JEFFREY G, additional, SPIEGLER, PETER A, additional, CHACHOUA, ABRAHAM, additional, MOORE, WILLIAM, additional, and STERMAN, DANIEL H, additional

Published
2023
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11. Supplementary File Table All (excel) from Lower Airway Dysbiosis Affects Lung Cancer Progression

Author

Tsay, Jun-Chieh J., primary, Wu, Benjamin G., primary, Sulaiman, Imran, primary, Gershner, Katherine, primary, Schluger, Rosemary, primary, Li, Yonghua, primary, Yie, Ting-An, primary, Meyn, Peter, primary, Olsen, Evan, primary, Perez, Luisannay, primary, Franca, Brendan, primary, Carpenito, Joseph, primary, Iizumi, Tadasu, primary, El-Ashmawy, Mariam, primary, Badri, Michelle, primary, Morton, James T., primary, Shen, Nan, primary, He, Linchen, primary, Michaud, Gaetane, primary, Rafeq, Samaan, primary, Bessich, Jamie L., primary, Smith, Robert L., primary, Sauthoff, Harald, primary, Felner, Kevin, primary, Pillai, Ray, primary, Zavitsanou, Anastasia-Maria, primary, Koralov, Sergei B., primary, Mezzano, Valeria, primary, Loomis, Cynthia A., primary, Moreira, Andre L., primary, Moore, William, primary, Tsirigos, Aristotelis, primary, Heguy, Adriana, primary, Rom, William N., primary, Sterman, Daniel H., primary, Pass, Harvey I., primary, Clemente, Jose C., primary, Li, Huilin, primary, Bonneau, Richard, primary, Wong, Kwok-Kin, primary, Papagiannakopoulos, Thales, primary, and Segal, Leopoldo N., primary

Published
2023
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12. Supplementary Table from Lower Airway Dysbiosis Affects Lung Cancer Progression

Author

Tsay, Jun-Chieh J., primary, Wu, Benjamin G., primary, Sulaiman, Imran, primary, Gershner, Katherine, primary, Schluger, Rosemary, primary, Li, Yonghua, primary, Yie, Ting-An, primary, Meyn, Peter, primary, Olsen, Evan, primary, Perez, Luisannay, primary, Franca, Brendan, primary, Carpenito, Joseph, primary, Iizumi, Tadasu, primary, El-Ashmawy, Mariam, primary, Badri, Michelle, primary, Morton, James T., primary, Shen, Nan, primary, He, Linchen, primary, Michaud, Gaetane, primary, Rafeq, Samaan, primary, Bessich, Jamie L., primary, Smith, Robert L., primary, Sauthoff, Harald, primary, Felner, Kevin, primary, Pillai, Ray, primary, Zavitsanou, Anastasia-Maria, primary, Koralov, Sergei B., primary, Mezzano, Valeria, primary, Loomis, Cynthia A., primary, Moreira, Andre L., primary, Moore, William, primary, Tsirigos, Aristotelis, primary, Heguy, Adriana, primary, Rom, William N., primary, Sterman, Daniel H., primary, Pass, Harvey I., primary, Clemente, Jose C., primary, Li, Huilin, primary, Bonneau, Richard, primary, Wong, Kwok-Kin, primary, Papagiannakopoulos, Thales, primary, and Segal, Leopoldo N., primary

Published
2023
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13. Supplementary Figure All from Lower Airway Dysbiosis Affects Lung Cancer Progression

Author

Tsay, Jun-Chieh J., primary, Wu, Benjamin G., primary, Sulaiman, Imran, primary, Gershner, Katherine, primary, Schluger, Rosemary, primary, Li, Yonghua, primary, Yie, Ting-An, primary, Meyn, Peter, primary, Olsen, Evan, primary, Perez, Luisannay, primary, Franca, Brendan, primary, Carpenito, Joseph, primary, Iizumi, Tadasu, primary, El-Ashmawy, Mariam, primary, Badri, Michelle, primary, Morton, James T., primary, Shen, Nan, primary, He, Linchen, primary, Michaud, Gaetane, primary, Rafeq, Samaan, primary, Bessich, Jamie L., primary, Smith, Robert L., primary, Sauthoff, Harald, primary, Felner, Kevin, primary, Pillai, Ray, primary, Zavitsanou, Anastasia-Maria, primary, Koralov, Sergei B., primary, Mezzano, Valeria, primary, Loomis, Cynthia A., primary, Moreira, Andre L., primary, Moore, William, primary, Tsirigos, Aristotelis, primary, Heguy, Adriana, primary, Rom, William N., primary, Sterman, Daniel H., primary, Pass, Harvey I., primary, Clemente, Jose C., primary, Li, Huilin, primary, Bonneau, Richard, primary, Wong, Kwok-Kin, primary, Papagiannakopoulos, Thales, primary, and Segal, Leopoldo N., primary

Published
2023
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14. Data from Lower Airway Dysbiosis Affects Lung Cancer Progression

Author

Tsay, Jun-Chieh J., primary, Wu, Benjamin G., primary, Sulaiman, Imran, primary, Gershner, Katherine, primary, Schluger, Rosemary, primary, Li, Yonghua, primary, Yie, Ting-An, primary, Meyn, Peter, primary, Olsen, Evan, primary, Perez, Luisannay, primary, Franca, Brendan, primary, Carpenito, Joseph, primary, Iizumi, Tadasu, primary, El-Ashmawy, Mariam, primary, Badri, Michelle, primary, Morton, James T., primary, Shen, Nan, primary, He, Linchen, primary, Michaud, Gaetane, primary, Rafeq, Samaan, primary, Bessich, Jamie L., primary, Smith, Robert L., primary, Sauthoff, Harald, primary, Felner, Kevin, primary, Pillai, Ray, primary, Zavitsanou, Anastasia-Maria, primary, Koralov, Sergei B., primary, Mezzano, Valeria, primary, Loomis, Cynthia A., primary, Moreira, Andre L., primary, Moore, William, primary, Tsirigos, Aristotelis, primary, Heguy, Adriana, primary, Rom, William N., primary, Sterman, Daniel H., primary, Pass, Harvey I., primary, Clemente, Jose C., primary, Li, Huilin, primary, Bonneau, Richard, primary, Wong, Kwok-Kin, primary, Papagiannakopoulos, Thales, primary, and Segal, Leopoldo N., primary

Published
2023
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15. Supplementary Figure Legends from Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy

Author

Sterman, Daniel H., primary, Alley, Evan, primary, Stevenson, James P., primary, Friedberg, Joseph, primary, Metzger, Susan, primary, Recio, Adri, primary, Moon, Edmund K., primary, Haas, Andrew R., primary, Vachani, Anil, primary, Katz, Sharyn I., primary, Sun, Jing, primary, Heitjan, Daniel F., primary, Hwang, Wei-Ting, primary, Litzky, Leslie, primary, Yearley, Jennifer H., primary, Tan, Kay See, primary, Papasavvas, Emmanouil, primary, Kennedy, Paul, primary, Montaner, Luis J., primary, Cengel, Keith A., primary, Simone, Charles B., primary, Culligan, Melissa, primary, Langer, Corey J., primary, and Albelda, Steven M., primary

Published
2023
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16. Supplementary Methods from Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy

Author

Sterman, Daniel H., primary, Alley, Evan, primary, Stevenson, James P., primary, Friedberg, Joseph, primary, Metzger, Susan, primary, Recio, Adri, primary, Moon, Edmund K., primary, Haas, Andrew R., primary, Vachani, Anil, primary, Katz, Sharyn I., primary, Sun, Jing, primary, Heitjan, Daniel F., primary, Hwang, Wei-Ting, primary, Litzky, Leslie, primary, Yearley, Jennifer H., primary, Tan, Kay See, primary, Papasavvas, Emmanouil, primary, Kennedy, Paul, primary, Montaner, Luis J., primary, Cengel, Keith A., primary, Simone, Charles B., primary, Culligan, Melissa, primary, Langer, Corey J., primary, and Albelda, Steven M., primary

Published
2023
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17. Supplemental Tables from Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy

Author

Sterman, Daniel H., primary, Alley, Evan, primary, Stevenson, James P., primary, Friedberg, Joseph, primary, Metzger, Susan, primary, Recio, Adri, primary, Moon, Edmund K., primary, Haas, Andrew R., primary, Vachani, Anil, primary, Katz, Sharyn I., primary, Sun, Jing, primary, Heitjan, Daniel F., primary, Hwang, Wei-Ting, primary, Litzky, Leslie, primary, Yearley, Jennifer H., primary, Tan, Kay See, primary, Papasavvas, Emmanouil, primary, Kennedy, Paul, primary, Montaner, Luis J., primary, Cengel, Keith A., primary, Simone, Charles B., primary, Culligan, Melissa, primary, Langer, Corey J., primary, and Albelda, Steven M., primary

Published
2023
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18. Supplementary Table 1 from A Live-Attenuated Listeria Vaccine (ANZ-100) and a Live-Attenuated Listeria Vaccine Expressing Mesothelin (CRS-207) for Advanced Cancers: Phase I Studies of Safety and Immune Induction

Author

Le, Dung T., primary, Brockstedt, Dirk G., primary, Nir-Paz, Ran, primary, Hampl, Johannes, primary, Mathur, Shruti, primary, Nemunaitis, John, primary, Sterman, Daniel H., primary, Hassan, Raffit, primary, Lutz, Eric, primary, Moyer, Bentley, primary, Giedlin, Martin, primary, Louis, Jana-Lynn, primary, Sugar, Elizabeth A., primary, Pons, Alice, primary, Cox, Andrea L., primary, Levine, Jordana, primary, Murphy, Aimee Luck, primary, Illei, Peter, primary, Dubensky, Thomas W., primary, Eiden, Joseph E., primary, Jaffee, Elizabeth M., primary, and Laheru, Daniel A., primary

Published
2023
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19. Supplementary Figure 2 from A Live-Attenuated Listeria Vaccine (ANZ-100) and a Live-Attenuated Listeria Vaccine Expressing Mesothelin (CRS-207) for Advanced Cancers: Phase I Studies of Safety and Immune Induction

Author

Le, Dung T., primary, Brockstedt, Dirk G., primary, Nir-Paz, Ran, primary, Hampl, Johannes, primary, Mathur, Shruti, primary, Nemunaitis, John, primary, Sterman, Daniel H., primary, Hassan, Raffit, primary, Lutz, Eric, primary, Moyer, Bentley, primary, Giedlin, Martin, primary, Louis, Jana-Lynn, primary, Sugar, Elizabeth A., primary, Pons, Alice, primary, Cox, Andrea L., primary, Levine, Jordana, primary, Murphy, Aimee Luck, primary, Illei, Peter, primary, Dubensky, Thomas W., primary, Eiden, Joseph E., primary, Jaffee, Elizabeth M., primary, and Laheru, Daniel A., primary

Published
2023
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20. Supplementary Figure 1 from A Live-Attenuated Listeria Vaccine (ANZ-100) and a Live-Attenuated Listeria Vaccine Expressing Mesothelin (CRS-207) for Advanced Cancers: Phase I Studies of Safety and Immune Induction

Author

Le, Dung T., primary, Brockstedt, Dirk G., primary, Nir-Paz, Ran, primary, Hampl, Johannes, primary, Mathur, Shruti, primary, Nemunaitis, John, primary, Sterman, Daniel H., primary, Hassan, Raffit, primary, Lutz, Eric, primary, Moyer, Bentley, primary, Giedlin, Martin, primary, Louis, Jana-Lynn, primary, Sugar, Elizabeth A., primary, Pons, Alice, primary, Cox, Andrea L., primary, Levine, Jordana, primary, Murphy, Aimee Luck, primary, Illei, Peter, primary, Dubensky, Thomas W., primary, Eiden, Joseph E., primary, Jaffee, Elizabeth M., primary, and Laheru, Daniel A., primary

Published
2023
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21. Supplementary Figure 3 from A Live-Attenuated Listeria Vaccine (ANZ-100) and a Live-Attenuated Listeria Vaccine Expressing Mesothelin (CRS-207) for Advanced Cancers: Phase I Studies of Safety and Immune Induction

Author

Le, Dung T., primary, Brockstedt, Dirk G., primary, Nir-Paz, Ran, primary, Hampl, Johannes, primary, Mathur, Shruti, primary, Nemunaitis, John, primary, Sterman, Daniel H., primary, Hassan, Raffit, primary, Lutz, Eric, primary, Moyer, Bentley, primary, Giedlin, Martin, primary, Louis, Jana-Lynn, primary, Sugar, Elizabeth A., primary, Pons, Alice, primary, Cox, Andrea L., primary, Levine, Jordana, primary, Murphy, Aimee Luck, primary, Illei, Peter, primary, Dubensky, Thomas W., primary, Eiden, Joseph E., primary, Jaffee, Elizabeth M., primary, and Laheru, Daniel A., primary

Published
2023
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22. Supplementary Figures from Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy

Author

Sterman, Daniel H., primary, Alley, Evan, primary, Stevenson, James P., primary, Friedberg, Joseph, primary, Metzger, Susan, primary, Recio, Adri, primary, Moon, Edmund K., primary, Haas, Andrew R., primary, Vachani, Anil, primary, Katz, Sharyn I., primary, Sun, Jing, primary, Heitjan, Daniel F., primary, Hwang, Wei-Ting, primary, Litzky, Leslie, primary, Yearley, Jennifer H., primary, Tan, Kay See, primary, Papasavvas, Emmanouil, primary, Kennedy, Paul, primary, Montaner, Luis J., primary, Cengel, Keith A., primary, Simone, Charles B., primary, Culligan, Melissa, primary, Langer, Corey J., primary, and Albelda, Steven M., primary

Published
2023
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25. Lung Microbial and Host Genomic Signatures as Predictors of Prognosis in Early-Stage Adenocarcinoma.

Author

Tsay JJ, Darawshy F, Wang C, Kwok B, Wong KK, Wu BG, Sulaiman I, Zhou H, Isaacs B, Kugler MC, Sanchez E, Bain A, Li Y, Schluger R, Lukovnikova A, Collazo D, Kyeremateng Y, Pillai R, Chang M, Li Q, Vanguri RS, Becker AS, Moore WH, Thurston G, Gordon T, Moreira AL, Goparaju CM, Sterman DH, Tsirigos A, Li H, Segal LN, and Pass HI

Subjects
Humans, Male, Female, Middle Aged, Prognosis, Aged, Neoplasm Recurrence, Local microbiology, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Biomarkers, Tumor genetics, Neoplasm Staging, Genomics methods, Lung Neoplasms genetics, Lung Neoplasms microbiology, Lung Neoplasms pathology, Adenocarcinoma of Lung genetics, Adenocarcinoma of Lung microbiology, Adenocarcinoma of Lung pathology
Abstract

Background: Risk of early-stage lung adenocarcinoma recurrence after surgical resection is significant, and the postrecurrence median survival is approximately 2 years. Currently, there are no commercially available biomarkers that predict recurrence. In this study, we investigated whether microbial and host genomic signatures in the lung can predict recurrence., Methods: In 91 patients with early-stage (stage IA/IB) lung adenocarcinoma with extensive follow-up, we used 16s rRNA gene sequencing and host RNA sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples., Results: Of 91 subjects, 23 had tumor recurrence over 5-year period. In tumor samples, lung adenocarcinoma recurrence was associated with enrichment in Dialister and Prevotella, whereas in unaffected lung samples, recurrence was associated with enrichment in Sphingomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with lung adenocarcinoma recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment in Stenotrophomonas geniculata and Chryseobacterium was positively correlated with upregulation of IL2, IL3, IL17, EGFR, and HIF1 signaling pathways among the host transcriptome. In tumor samples, enrichment in Veillonellaceae (Dialister), Ruminococcaceae, Haemophilus influenzae, and Neisseria was positively correlated with upregulation of IL1, IL6, IL17, IFN, and tryptophan metabolism pathways., Conclusions: Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC = 0.83)., Impact: This study suggests that lung adenocarcinoma recurrence is associated with distinct pathophysiologic mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor., (©2024 American Association for Cancer Research.)

Published
2024
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26. The evolution of lung adenocarcinoma precursors is associated with chromosomal instability and transition from innate to adaptive immune response/evasion.

Author

Hu X, Zhu B, Vokes N, Fujimoto J, Rojas Alvarez FR, Heeke S, Moreira AL, Solis LM, Haymaker C, Velcheti V, Sterman DH, Pass HI, Cheng C, Lee JJ, Zhang J, Wei Z, Wu J, Le X, Ostrin E, Toumazis I, Gibbons D, Su D, Fukuoka J, Antonoff MB, Gerber DE, Li C, Kadara H, Wang L, Davis M, Heymach JV, Hannash S, Wistuba I, Dubinett S, Alexandrov L, Lippman S, Spira A, Futreal AP, Reuben A, and Zhang J

Abstract

Studying lung adenocarcinoma (LUAD) early carcinogenesis is challenging, primarily due to the lack of LUAD precursors specimens. We amassed multi-omics data from 213 LUAD and LUAD precursors to identify molecular features underlying LUAD precancer evolution. We observed progressively increasing mutations, chromosomal aberrations, whole genome doubling and genomic instability from precancer to invasive LUAD, indicating aggravating chromosomal instability (CIN). Telomere shortening, a crucial genomic alteration linked to CIN, emerged at precancer stage. Moreover, later-stage lesions demonstrated increasing cancer stemness and decreasing alveolar identity, suggesting epithelial de-differentiation during early LUAD carcinogenesis. The innate immune cells progressively diminished from precancer to invasive LUAD, concomitant with a gradual recruitment of adaptive immune cells (except CD8 + and gamma-delta T cells that decreased in later stages) and upregulation of numerous immune checkpoints, suggesting LUAD precancer evolution is associated with a shift from innate to adaptive immune response and immune evasion mediated by various mechanisms., Competing Interests: J.J.Z. reports research funding from Merck, Johnson and Johnson, Novartis, Summit, Hengenix and consultant fees from BMS, Johnson and Johnson, AstraZeneca, Geneplus, OrigMed, Innovent, Varian, Catalyst outside the submitted work. I.I.W reports Honoraria from Genentech/Roche, Bayer, Bristol-Myers Squibb, Astra Zeneca/Medimmune, Pfizer, HTG Molecular, Asuragen, Merck, GlaxoSmithKline, Guardant Health, Oncocyte, Flame, and MSD; Research support from Genentech, Oncoplex, HTG Molecular, DepArray, Merck, Bristol-Myers Squibb, Medimmune, Adaptive, Adapt immune, EMD Serono, Pfizer, Takeda, Amgen, Karus, Johnson & Johnson, Bayer, Iovance, 4D, Novartis, and Akoya. J.V.H. reports honorariums from AstraZeneca, Boehringer-Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Guardant Health, Foundation medicine, Hengrui Therapeutics, Eli Lilly, Novartis, Spectrum, EMD Serono, Sanofi, Takeda, Mirati Therapeutics, BMS, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, EMD Serono, Pneuma Respiratory, Kairos Venture Investments, Roche and Leads Biolabs. D.E.G. reports research funding from Astra-Zeneca, BerGenBio, Karyopharm, and Novocure; stock ownership in Gilead; consultant/advisory fees from Abbvie, Astra-Zeneca, Catalyst Pharmaceuticals, Daiichi-Sankyo, Elevation Oncology, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Regeneron Pharmaceuticals, and Sanofi; and serving as co-founder and chief scientific officer of OncoSeer Diagnostics, Inc. S.H. reports consulting fees from Guardant Health and AstraZeneca. S.M.D serves on the Scientific Advisory Boards for Early Diagnostics Inc. and LungLife AI, Inc. and has received research funding from Johnson & Johnson Lung Cancer Initiative and Novartis. The other authors declare no competing interests.

Published
2024
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27. Role of small airway dysfunction in unexplained exertional dyspnoea.

Author

Sharpe AL, Reibman J, Oppenheimer BW, Goldring RM, Liu M, Shao Y, Bohart I, Kwok B, Weinstein T, Addrizzo-Harris D, Sterman DH, and Berger KI

Abstract

Background: Isolated small airway abnormalities may be demonstrable at rest in patients with normal spirometry; however, the relationship of these abnormalities to exertional symptoms remains uncertain. This study uses an augmented cardiopulmonary exercise test (CPET) to include evaluation of small airway function during and following exercise to unmask abnormalities not evident with standard testing in individuals with dyspnoea and normal spirometry., Methods: Three groups of subjects were studied: 1) World Trade Center (WTC) dust exposure (n=20); 2) Clinical Referral (n=15); and Control (n=13). Baseline evaluation included respiratory oscillometry. Airway function during an incremental workload CPET was assessed by: 1) tidal flow versus volume curves during exercise to assess for dynamic hyperinflation and expiratory flow limitation; and 2) post-exercise spirometry and oscillometry to evaluate for airway hyperreactivity., Results: All subjects demonstrated normal baseline forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC). Dyspnoea was reproduced during CPET in WTC and Clinical Referral groups versus Control without abnormality in respiratory pattern and minute ventilation. Tidal flow-volume curves uncovered expiratory flow limitation and/or dynamic hyperinflation with increased prevalence in WTC and Clinical Referral versus Control (55%, 87% versus 15%; p<0.001). Post-exercise oscillometry uncovered small airway hyperreactivity with increased prevalence in WTC and Clinical Referral versus Control (40%, 47% versus 0%, p < 0.05)., Conclusions: We uncovered mechanisms for exertional dyspnoea in subject with normal spirometry that was attributable to either small airway dysfunction during exercise and/or small airway hyperreactivity following exercise. The similarity of findings in WTC environmentally exposed and clinically referred cohorts suggests broad relevance for these evaluations., Competing Interests: Conflict of interest: None of the authors have a conflict of interest to declare., (Copyright ©The authors 2023.)

Published
2023
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