Publications by authors named "Iazsmin Bauer Ventura"

6 Publications

  • Page 1 of 1

Characteristics and Prevalence of Domestic and Occupational Inhalational Exposures Across Interstitial Lung Diseases.

Chest 2021 Feb 20. Epub 2021 Feb 20.

Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, IL.

Background: Inhalational exposures are increasingly recognized as contributing factors in interstitial lung disease (ILD). However, the characteristics of both exposures and exposed patients are not well understood. We hypothesized that domestic and occupational inhalational exposures would be common and associated with differences in demographics, clinical characteristics, and transplant-free survival in patients with all forms of ILD.

Research Question: What is the prevalence of inhalational exposures across all ILD diagnoses, and are these exposures associated with differences in demographics, clinical characteristics, and transplant-free survival?

Study Design And Methods: Patients from a tertiary ILD clinic underwent an interview designed to capture inhalational exposures including occupational, home, hobbies, and tobacco. Demographic and survival data were collected from the electronic medical record. Survival analysis was performed using Cox regression to compare exposed versus unexposed patients and adjusted for gender, age, physiology (GAP) score and smoking.

Results: One hundred fifty-six patients seen between May and October 2018 were analyzed. Patients had a wide variety of multidisciplinary diagnoses (MDD), with a minority (14%) of patients with hypersensitivity pneumonitis (HP). One hundred and one (65%) patients had potentially relevant inhalational exposures. More men than women had a history of any exposure (82% versus 51%, p<0.001), occupational exposure (66% versus 14%, p<0.001) and multiple exposures (56% versus 26%, p<0.001). White race was associated with bird and hobby exposure. Patients with any exposure had worse transplant-free survival (unadjusted HR=2.58, 95%CI=1.13-5.92, P=0.025), but this was not statistically significant after adjustment (HR=1.82, 95%CI=0.77-4.27, P=0.17).

Interpretation: A standardized interview revealed a majority of patients across all types of ILD had potentially relevant inhalational exposures. Exposures were markedly different based on demographics and were associated with worse transplant-free survival, but this survival difference was not significant after multivariable adjustment. Identification and avoidance of exposures represent actionable targets in ILD management.
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http://dx.doi.org/10.1016/j.chest.2021.02.026DOI Listing
February 2021

COVIDOSE: A Phase II Clinical Trial of Low-Dose Tocilizumab in the Treatment of Noncritical COVID-19 Pneumonia.

Clin Pharmacol Ther 2021 03 10;109(3):688-696. Epub 2020 Dec 10.

Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, Illinois, USA.

Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the mortality of coronavirus disease 2019 (COVID-19). The IL-6 receptor-blocking monoclonal antibody tocilizumab has been repurposed for COVID-19, but prospective trials and dose-finding studies in COVID-19 have not yet fully reported. We conducted a single-arm phase II trial of low-dose tocilizumab in nonintubated hospitalized adult patients with COVID-19, radiographic pulmonary infiltrate, fever, and C-reactive protein (CRP) ≥ 40 mg/L. We hypothesized that doses significantly lower than the emerging standards of 400 mg or 8 mg/kg would resolve clinical and laboratory indicators of hyperinflammation. A dose range from 40 to 200 mg was evaluated, with allowance for one repeat dose at 24 to 48 hours. The primary objective was to assess the relationship of dose to fever resolution and CRP response. Thirty-two patients received low-dose tocilizumab, with the majority experiencing fever resolution (75%) and CRP decline consistent with IL-6 pathway abrogation (86%) in the 24-48 hours following drug administration. There was no evidence of a relationship between dose and fever resolution or CRP decline over the dose range of 40-200 mg. Within the 28-day follow-up, 5 (16%) patients died. For patients who recovered, median time to clinical recovery was 3 days (interquartile range, 2-5). Clinically presumed and/or cultured bacterial superinfections were reported in 5 (16%) patients. Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with COVID-19. Results of this trial provide rationale for a randomized, controlled trial of low-dose tocilizumab in COVID-19.
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http://dx.doi.org/10.1002/cpt.2117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753375PMC
March 2021

COVIDOSE: Low-dose tocilizumab in the treatment of Covid-19.

medRxiv 2020 Jul 26. Epub 2020 Jul 26.

Background Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the high mortality of coronavirus disease 2019 (Covid-19). Tocilizumab, an IL-6 receptor blocking monoclonal antibody, has been repurposed for Covid-19, but prospective trials and dose-finding studies in Covid-19 are lacking. Methods We conducted a phase 2 trial of low-dose tocilizumab in hospitalized adult patients with Covid-19, radiographic pulmonary infiltrate, fever, and C-reactive protein (CRP) >= 40 mg/L who did not require mechanical ventilation. Dose cohorts were determined by a trial Operations Committee, stratified by CRP and epidemiologic risk factors. A range of doses from 40 to 200 mg (low-dose tocilizumab) was evaluated, with allowance for one repeat dose at 24-48 hours. The primary objective was to assess the relationship of dose to fever resolution and CRP response. Outcomes were compared with retrospective controls with Covid-19. Correlative studies evaluating host antibody response were performed in parallel. Findings A total of 32 patients received low-dose tocilizumab. This cohort had improved fever resolution (75.0% vs. 34.2%, p = 0.001) and CRP decline (86.2% vs. 14.3%, p < 0.001) in the 24-48 hours following drug administration, as compared to the retrospective controls (N=41). The probabilities of fever resolution or CRP decline did not appear to be dose-related in this small study (p=0.80 and p=0.10, respectively). Within the 28-day follow-up, 5 (15.6%) patients died. For patients who recovered, median time to clinical recovery was 3 days (IQR, 2-5). Clinically presumed and/or cultured bacterial superinfections were reported in 5 (15.6%) patients. Correlative biological studies demonstrated that tocilizumab-treated patients produced anti-SARS-CoV-2 antibodies comparable to controls. Interpretation Low-dose tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with Covid-19. Results of this trial and its correlative biological studies provide rationale for a randomized, controlled trial of low-dose tocilizumab in Covid-19.
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http://dx.doi.org/10.1101/2020.07.20.20157503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7386518PMC
July 2020

Myositis-specific Antibodies Identify A Distinct Interstitial Pneumonia with Autoimmune Features Phenotype.

Eur Respir J 2020 Jul 16. Epub 2020 Jul 16.

Department of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University of California at Davis

Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an anti-synthetase syndrome. Whether MSAs and myositis associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear.A multi-center, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis (IPF) and non-IIM CTD-ILDs. The primary endpoint assessed was three-year transplant-free survival. Two hundred sixty-nine patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.
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http://dx.doi.org/10.1183/13993003.01205-2020DOI Listing
July 2020

Association of Black Race with Outcomes in COVID-19 Disease: A Retrospective Cohort Study.

Ann Am Thorac Soc 2020 10;17(10):1336-1339

University of Chicago Chicago, Illinois.

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http://dx.doi.org/10.1513/AnnalsATS.202006-583RLDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7640625PMC
October 2020

Prevalence and Clinical Significance of Antineutrophil Cytoplasmic Antibodies in North American Patients With Idiopathic Pulmonary Fibrosis.

Chest 2019 10 7;156(4):715-723. Epub 2019 Jun 7.

Department of Internal Medicine, University of California San Francisco, San Francisco, CA; Department of Pulmonary and Critical Care Medicine, Kaiser Permanente San Francisco, San Francisco, CA. Electronic address:

Background: Antineutrophil cytoplasmic antibodies (ANCAs) have been reported to occur in 7% to 10% of patients with idiopathic pulmonary fibrosis (IPF), but their clinical relevance remains unclear. The aim of this study was to estimate the prevalence of ANCAs in a North American population with IPF and evaluate their clinical significance.

Methods: This was a retrospective study of two independent cohorts of patients diagnosed with IPF at the University of California San Francisco (discovery cohort) and the University of Chicago (replication cohort). Myeloperoxidase (MPO) and proteinase 3 (PR3) ANCAs were measured in all patients. Prevalence and associations of ANCAs with clinical characteristics and transplant-free survival were evaluated.

Results: A total of 14 of 353 (4.0%; 95% CI, 2.2-6.5) and 20 of 392 (5.1%; 95% CI, 3.1-7.8) patients with IPF were positive for ANCAs at the time of diagnosis in the discovery and replication cohorts, respectively. Among those positive for MPO antibodies, two of six (33%) in the discovery cohort and three of 12 (25%) in the replication cohort developed vasculitis. None of the patients who were PR3-positive developed vasculitis. Patients who were ANCA-positive were more likely to be women than patients who were ANCA-negative, and were more likely to have some ground-glass opacities on CT scan. In the combined cohort of 745 patients, median transplant-free survival was not significantly different in patients who were ANCA-positive vs ANCA-negative (P = .57).

Conclusions: ANCA positivity is uncommon in North American patients with IPF and not associated with baseline disease severity or transplant-free survival; however, a significant proportion of patients who are MPO-positive with IPF develop clinical vasculitis.
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http://dx.doi.org/10.1016/j.chest.2019.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859239PMC
October 2019