Browsing by Author "Giovacchini, Coral X"

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    Clinical and radiographic predictors of successful therapeutic bronchoscopy for the relief of malignant central airway obstruction.
    (BMC pulmonary medicine, 2019-11) Giovacchini, Coral X; Kessler, Edward R; Merrick, Christopher M; Gao, Junheng; Wang, Xiaofei; Wahidi, Momen M; Shofer, Scott L; Cheng, George Z; Mahmood, Kamran
    BACKGROUND:Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO. METHODS:We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival. RESULTS:During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015). CONCLUSIONS:Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.
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    Immuno-fibrotic drivers of impaired lung function in post-COVID-19 syndrome.
    (medRxiv, 2021-02-06) Chun, Hyung J; Coutavas, Elias; Pine, Alexander; Lee, Alfred I; Yu, Vanessa; Shallow, Marcus; Giovacchini, Coral X; Mathews, Anne; Stephenson, Brian; Que, Loretta G; Lee, Patty J; Kraft, Bryan D
    Introduction: Subjects recovering from COVID-19 frequently experience persistent respiratory ailments; however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity. Methods: We performed a prospective cohort study of subjects with persistent symptoms after recovering from acute COVID-19 illness, collecting clinical data, pulmonary function tests, and blood. Plasma samples were used for multiplex profiling of circulating factors associated with inflammation, metabolism, angiogenesis, and fibrosis. Results: Sixty-one subjects were enrolled across two academic medical centers at a median of 9 weeks (interquartile range 6-10) after COVID-19 illness: n=13 subjects (21%) mild/non-hospitalized, n=30 (49%) hospitalized/non-critical, and n=18 subjects (30%) hospitalized/intensive care ("ICU"). Fifty-three subjects (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P<0.05), but did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered subjects by past COVID-19 severity. Lipocalin 2 (LCN2), matrix metalloproteinase-7 (MMP-7), and hepatocyte growth factor (HGF) identified by the model were significantly higher in the ICU group (P<0.05) and inversely correlated with FVC and DLCO (P<0.05). Conclusions: Subjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets. Funding: The study was funded in part by the NHLBI (K08HL130557 to BDK and R01HL142818 to HJC), the DeLuca Foundation Award (AP), a donation from Jack Levin to the Benign Hematology Program at Yale, and Divisional/Departmental funds from Duke University.
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    Immunofibrotic drivers of impaired lung function in postacute sequelae of SARS-CoV-2 infection.
    (JCI insight, 2021-07-22) Chun, Hyung J; Coutavas, Elias; Pine, Alexander B; Lee, Alfred I; Yu, Vanessa L; Shallow, Marcus K; Giovacchini, Coral X; Mathews, Anne M; Stephenson, Brian; Que, Loretta G; Lee, Patty J; Kraft, Bryan D
    BACKGROUNDIndividuals recovering from COVID-19 frequently experience persistent respiratory ailments, which are key elements of postacute sequelae of SARS-CoV-2 infection (PASC); however, little is known about the underlying biological factors that may direct lung recovery and the extent to which these are affected by COVID-19 severity.METHODSWe performed a prospective cohort study of individuals with persistent symptoms after acute COVID-19, collecting clinical data, pulmonary function tests, and plasma samples used for multiplex profiling of inflammatory, metabolic, angiogenic, and fibrotic factors.RESULTSSixty-one participants were enrolled across 2 academic medical centers at a median of 9 weeks (interquartile range, 6-10 weeks) after COVID-19 illness: n = 13 participants (21%) had mild COVID-19 and were not hospitalized, n = 30 participants (49%) were hospitalized but were considered noncritical, and n = 18 participants (30%) were hospitalized and in the intensive care unit (ICU). Fifty-three participants (85%) had lingering symptoms, most commonly dyspnea (69%) and cough (58%). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and diffusing capacity for carbon monoxide (DLCO) declined as COVID-19 severity increased (P < 0.05) but these values did not correlate with respiratory symptoms. Partial least-squares discriminant analysis of plasma biomarker profiles clustered participants by past COVID-19 severity. Lipocalin-2 (LCN2), MMP-7, and HGF identified by our analysis were significantly higher in the ICU group (P < 0.05), inversely correlated with FVC and DLCO (P < 0.05), and were confirmed in a separate validation cohort (n = 53).CONCLUSIONSubjective respiratory symptoms are common after acute COVID-19 illness but do not correlate with COVID-19 severity or pulmonary function. Host response profiles reflecting neutrophil activation (LCN2), fibrosis signaling (MMP-7), and alveolar repair (HGF) track with lung impairment and may be novel therapeutic or prognostic targets.FundingNational Heart, Lung, and Blood Institute (K08HL130557 and R01HL142818), American Heart Association (Transformational Project Award), the DeLuca Foundation Award, a donation from Jack Levin to the Benign Hematology Program at Yale University, and Duke University.