Try a new search

Format these results:

Searched for:

person:weidem01

in-biosketch:yes

Total Results:

214


Lower Airway Dysbiosis Augments Lung Inflammatory Injury in Mild-to-Moderate Chronic Obstructive Pulmonary Disease

Sulaiman, Imran; Wu, Benjamin G; Chung, Matthew; Isaacs, Bradley; Tsay, Jun-Chieh J; Holub, Meredith; Barnett, Clea R; Kwok, Benjamin; Kugler, Matthias C; Natalini, Jake G; Singh, Shivani; Li, Yonghua; Schluger, Rosemary; Carpenito, Joseph; Collazo, Destiny; Perez, Luisanny; Kyeremateng, Yaa; Chang, Miao; Campbell, Christina D; Hansbro, Philip M; Oppenheimer, Beno W; Berger, Kenneth I; Goldring, Roberta M; Koralov, Sergei B; Weiden, Michael D; Xiao, Rui; D'Armiento, Jeanine; Clemente, Jose C; Ghedin, Elodie; Segal, Leopoldo N
PMID: 37677136
ISSN: 1535-4970
CID: 5606572

Association of Lung Function Decline with All-Cause and Cancer-Cause Mortality after World Trade Center Dust Exposure

Goldfarb, David G; Hall, Charles B; Choi, Jaeun; Zeig-Owens, Rachel; Cohen, Hillel W; Cannon, Madeline; Prezant, David J; Weiden, Michael D
PMCID:10405606
PMID: 36961515
ISSN: 2325-6621
CID: 5592272

Relationship between low serum IgE levels and malignancies in 9/11 World Trade Center responders

Ferastraoaru, Denisa; Zeig-Owens, Rachel; Goldfarb, David G; Mueller, Alexandra K; Hall, Charles B; Weiden, Michael D; Schwartz, Theresa; Prezant, David J; Rosenstreich, David
BACKGROUND:Individuals with very low immunoglobulin E-(IgE)-levels have a high risk of developing malignancy. Previous studies have shown that World Trade Center (WTC)-responders exposed to carcinogens have an elevated risk of some cancers. OBJECTIVE:To evaluate the association between low-serum IgE levels and cancer development in WTC-exposed-responders. METHODS:IgE-levels were measured in 1,851 WTC-responders after 9/11/2001. This is the first pilot study in humans comparing the odds of developing cancer in this high-risk population, between the "low-IgE" (IgE in the lowest 3 rd percentile) versus "non-low IgE" participants. RESULTS:A significantly higher proportion of hematologic malignancies was found in low-IgE (4/55, 7.3%) compared with non-low IgE (26/1,796, 1.5%, p<0.01) responders. The proportion of solid tumors were similar in both groups (5.5% vs 11.4%, p>0.05). After adjustment for relevant confounders (race, sex, age at blood draw, WTC-arrival time, smoking status), the low-IgE-participants had 7.81 times greater odds (95% CI=1.77-29.35) of developing hematologic cancer when compared with non-low-IgE-participants. The hematologic cancers found in this cohort were leukemia (n=1), multiple myeloma (n=1) and lymphoma (n=2). No statistical significance was found when estimating the odds-ratio for solid tumors in relation to IgE levels. CONCLUSION/CONCLUSIONS:WTC-responders with low serum IgE levels had the highest odds of developing hematologic malignancies. This hypothesis-generating study suggests that low serum IgE levels might be associated with the development of specific malignancies in at-risk individuals exposed to carcinogens. Larger, multicenter studies with adequate follow up of individuals with different IgE levels are needed to better evaluate this relationship.
PMID: 35872243
ISSN: 1534-4436
CID: 5276112

High burden of clonal hematopoiesis in first responders exposed to the World Trade Center disaster

Jasra, Sakshi; Giricz, Orsi; Zeig-Owens, Rachel; Pradhan, Kith; Goldfarb, David G; Barreto-Galvez, Angelica; Silver, Alexander J; Chen, Jiahao; Sahu, Srabani; Gordon-Mitchell, Shanisha; Choudhary, Gaurav S; Aluri, Srinivas; Bhagat, Tushar D; Shastri, Aditi; Bejan, Cosmin A; Stockton, Shannon S; Spaulding, Travis P; Thiruthuvanathan, Victor; Goto, Hiroki; Gerhardt, Jeannine; Haider, Syed Hissam; Veerappan, Arul; Bartenstein, Matthias; Nwankwo, George; Landgren, Ola; Weiden, Michael D; Lekostaj, Jacqueline; Bender, Ryan; Fletcher, Frederick; Greenberger, Lee; Ebert, Benjamin L; Steidl, Ulrich; Will, Britta; Nolan, Anna; Madireddy, Advaitha; Savona, Michael R; Prezant, David J; Verma, Amit
The terrorist attacks on the World Trade Center (WTC) created an unprecedented environmental exposure to aerosolized dust, gases and potential carcinogens. Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. Here we show that deep targeted sequencing of blood samples identified a significantly higher proportion of WTC-exposed first responders with CH (10%; 48 out of 481) when compared with non-WTC-exposed firefighters (6.7%; 17 out of 255; odds ratio, 3.14; 95% confidence interval, 1.64-6.03; P = 0.0006) after controlling for age, sex and race/ethnicity. The frequency of somatic mutations in WTC-exposed first responders showed an age-related increase and predominantly affected DNMT3A, TET2 and other CH-associated genes. Exposure of lymphoblastoid cells to WTC particulate matter led to dysregulation of DNA replication at common fragile sites in vitro. Moreover, mice treated with WTC particulate matter developed an increased burden of mutations in hematopoietic stem and progenitor cell compartments. In summary, the high burden of CH in WTC-exposed first responders provides a rationale for enhanced screening and preventative efforts in this population.
PMID: 35256801
ISSN: 1546-170x
CID: 5180942

Twenty-Year Reflection on the Impact of World Trade Center Exposure on Pulmonary Outcomes in Fire Department of the City of New York (FDNY) Rescue and Recovery Workers

Cleven, Krystal L; Rosenzvit, Carla; Nolan, Anna; Zeig-Owens, Rachel; Kwon, Sophia; Weiden, Michael D; Skerker, Molly; Halpren, Allison; Prezant, David J
After the terrorist attacks on September 11, 2001 (9/11), many rescue/recovery workers developed respiratory symptoms and pulmonary diseases due to their extensive World Trade Center (WTC) dust cloud exposure. Nearly all Fire Department of the City of New York (FDNY) workers were present within 48 h of 9/11 and for the next several months. Since the FDNY had a well-established occupational health service for its firefighters and Emergency Medical Services workers prior to 9/11, the FDNY was able to immediately start a rigorous monitoring and treatment program for its WTC-exposed workers. As a result, respiratory symptoms and diseases were identified soon after 9/11. This focused review summarizes the WTC-related respiratory diseases that developed in the FDNY cohort after 9/11, including WTC cough syndrome, obstructive airways disease, accelerated lung function decline, airway hyperreactivity, sarcoidosis, and obstructive sleep apnea. Additionally, an extensive array of biomarkers has been identified as associated with WTC-related respiratory disease. Future research efforts will not only focus on further phenotyping/treating WTC-related respiratory disease but also on additional diseases associated with WTC exposure, especially those that take decades to develop, such as cardiovascular disease, cancer, and interstitial lung disease.
PMCID:8583580
PMID: 34766209
ISSN: 1432-1750
CID: 5050772

Lung function decline before and after treatment of World Trade Center associated obstructive airways disease with inhaled corticosteroids and long-acting beta agonists

Goldfarb, David G; Putman, Barbara; Lahousse, Lies; Zeig-Owens, Rachel; Vaeth, Brandon M; Schwartz, Theresa; Hall, Charles B; Prezant, David J; Weiden, Michael D
BACKGROUND:-trajectory in this population is unknown. METHODS:-slope pre- and post-treatment. RESULTS:-slope improvement (7.9 ml/year, 95% CI: -0.5 to 17.2). CONCLUSIONS:-decline who have not responded to ICS/LABA.
PMID: 34254700
ISSN: 1097-0274
CID: 4938372

Serum Th-2 cytokines and FEV1 decline in WTC-exposed firefighters: A 19-year longitudinal study

Weiden, Michael D; Singh, Ankura; Goldfarb, David G; Putman, Barbara; Zeig-Owens, Rachel; Schwartz, Theresa; Cohen, Hillel W; Prezant, David J
BACKGROUND:-decline. METHODS:decline rates were analyzed using multivariable linear regression controlling for demographics, smoking status, and other potential confounders. RESULTS:decline rate (-4.0 ± 1.6 ml/year per IL-4 doubling). CONCLUSIONS:decline/year. Drugs targeting the IL-4 pathway may improve lung function in this high-risk subgroup.
PMID: 34288008
ISSN: 1097-0274
CID: 4948252

Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome

Sulaiman, Imran; Chung, Matthew; Angel, Luis; Tsay, Jun-Chieh J; Wu, Benjamin G; Yeung, Stephen T; Krolikowski, Kelsey; Li, Yonghua; Duerr, Ralf; Schluger, Rosemary; Thannickal, Sara A; Koide, Akiko; Rafeq, Samaan; Barnett, Clea; Postelnicu, Radu; Wang, Chang; Banakis, Stephanie; Pérez-Pérez, Lizzette; Shen, Guomiao; Jour, George; Meyn, Peter; Carpenito, Joseph; Liu, Xiuxiu; Ji, Kun; Collazo, Destiny; Labarbiera, Anthony; Amoroso, Nancy; Brosnahan, Shari; Mukherjee, Vikramjit; Kaufman, David; Bakker, Jan; Lubinsky, Anthony; Pradhan, Deepak; Sterman, Daniel H; Weiden, Michael; Heguy, Adriana; Evans, Laura; Uyeki, Timothy M; Clemente, Jose C; de Wit, Emmie; Schmidt, Ann Marie; Shopsin, Bo; Desvignes, Ludovic; Wang, Chan; Li, Huilin; Zhang, Bin; Forst, Christian V; Koide, Shohei; Stapleford, Kenneth A; Khanna, Kamal M; Ghedin, Elodie; Segal, Leopoldo N
Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2.
PMID: 34465900
ISSN: 2058-5276
CID: 4998422

Functional lower airways genomic profiling of the microbiome to capture active microbial metabolism

Sulaiman, Imran; Wu, Benjamin G; Li, Yonghua; Tsay, Jun-Chieh; Sauthoff, Maya; Scott, Adrienne S; Ji, Kun; Koralov, Sergei B; Weiden, Michael; Clemente, Jose; Jones, Drew; Huang, Yvonne J; Stringer, Kathleen A; Zhang, Lingdi; Geber, Adam; Banakis, Stephanie; Tipton, Laura; Ghedin, Elodie; Segal, Leopoldo N
RATIONALE/BACKGROUND:Microbiome studies of the lower airway based on bacterial 16S rRNA gene sequencing assess microbial community structure but can only infer functional characteristics. Microbial products, such as short chain fatty acids (SCFAs), in the lower airways have significant impact on the host's immune tone. Thus, functional approaches to the analyses of the microbiome are necessary. METHODS:Here we used upper and lower airway samples from a research bronchoscopy smoker cohort. In addition, we validated our results in an experimental mouse model. MEASUREMENTS/METHODS:We extended our microbiota characterisation beyond 16S rRNA gene sequencing with the use of whole genome (WGS) and RNA metatranscriptome sequencing. Short chain fatty acids (SCFA) were also measured in lower airway samples and correlated with each of the sequencing datasets. In the mouse model, 16S rRNA gene and RNA metatranscriptome sequencing were performed. MAIN RESULTS/RESULTS:Functional evaluations of the lower airway microbiota using inferred metagenome, WGS and metatranscriptome were dissimilar. Comparison with measured levels of SCFAs shows that the inferred metagenome from the 16S rRNA gene sequencing data was poorly correlated, while better correlations were noted when SCFAs levels were compared with WGS and metatranscriptome. Modelling lower airway aspiration with oral commensals in a mouse model showed that the metatranscriptome most efficiently captures transient active microbial metabolism, which was overestimated by 16S rRNA gene sequencing. CONCLUSIONS:Functional characterisation of the lower airway microbiota through metatranscriptome identify metabolically active organisms capable of producing metabolites with immunomodulatory capacity such as SCFAs.
PMID: 33446604
ISSN: 1399-3003
CID: 4747282

Episodic Aspiration with Oral Commensals Induces a MyD88-dependent, Pulmonary Th17 Response that Mitigates Susceptibility to Streptococcus pneumoniae

Wu, Benjamin G; Sulaiman, Imran; Tsay, Jun-Chieh J; Perez, Luisanny; Franca, Brendan; Li, Yonghua; Wang, Jing; Gonzalez, Amber N; El-Ashmawy, Mariam; Carpenito, Joseph; Olsen, Evan; Sauthoff, Maya; Yie, Kevin; Liu, Xiuxiu; Shen, Nan; Clemente, Jose C; Kapoor, Bianca; Zangari, Tonia; Mezzano, Valeria; Loomis, Cynthia; Weiden, Michael D; Koralov, Sergei; D'Armiento, Jeanine; Ahuja, Sunil K; Wu, Xue-Ru; Weiser, Jeffrey N; Segal, Leopoldo N
Rationale Cross-sectional human data suggest that enrichment of oral anaerobic bacteria in the lung is associated with increased Th17 inflammatory phenotype. In this study we evaluated the microbial and host immune response dynamics after aspiration with a oral commensals using a preclinical mouse model. Methods Aspiration with a mixture of human oral commensals (MOC; Prevotella melaninogenica, Veillonella parvula, and Streptococcus mitis) was modeled in mice followed by variable time of sacrifice. Genetic background of mice included WT, MyD88 knock out and STAT3C. Measurements 16S rRNA gene sequencing characterized changes in microbiota. Flow cytometry, cytokine measurement via Luminex and RNA host transcriptome sequencing was used to characterize host immune phenotype. Main Results While MOC aspiration correlated with lower airway dysbiosis that resolved within five days, it induced an extended inflammatory response associated with IL17-producing T-cells lasting at least 14 days. MyD88 expression was required for the IL-17 response to MOC aspiration, but not for T-cell activation or IFN-γ expression. MOC aspiration prior to a respiratory challenge with S. pneumoniae led to a decreased in host's susceptibility to this pathogen. Conclusions Thus, in otherwise healthy mice, a single aspiration event with oral commensals are rapidly cleared from the lower airways, but induce a prolonged Th17 response that secondarily decreased susceptibility to respiratory pathogens. Translationally, these data implicate an immuno-protective role of episodic microaspiration of oral microbes in the regulation of the lung immune phenotype and mitigation of host susceptibility to infection with lower airway pathogens.
PMID: 33166473
ISSN: 1535-4970
CID: 4664852