Judith A Voynow

Virginia Commonwealth University, Ричмонд, Virginia, United States

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Publications (65)247.76 Total impact

  • M L Meyer · E N Potts-Kant · A J Ghio · B M Fischer · W M Foster · J A Voynow ·

    AJP Lung Cellular and Molecular Physiology 07/2015; 309(1):L98. DOI:10.1152/ajplung.zh5-6794-corr.2015 · 4.08 Impact Factor
  • Judith A. Voynow · Richard Auten ·
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    ABSTRACT: In this review, we discuss the impact of environmental tobacco smoke and particulate and gaseous air pollutants derived from fossil fuel combustion on a particularly vulnerable population, infants, and children. Indoor and outdoor air pollutants exacerbate chronic respiratory diseases and lower respiratory tract infections. However, there is an even more alarming impact of antenatal air pollution exposures. There are several reports in rodents and monkeys that maternal exposure to tobacco smoke or fossil fuel-generated air pollutants causes in utero growth retardation, lung remodeling, and immune cell activation that increases the risk for asthma or the risk of morbidity with respiratory infections. Importantly, epidemiologic studies confirm that maternal exposure to air pollutants decreases lung function in infants and children which may persist to young adulthood. Thus, environmental air pollutants contribute to childhood origins of chronic obstructive lung disease by changing the capacity for normal lung development and repair, by promoting early lung inflammation that increases the susceptibility to pollution-triggered symptomatic lung disease in adulthood, and by limiting the capacity for later adaptive/repair responses to environmental and infectious insults.
    Clinical Pulmonary Medicine 07/2015; 22(4):177-184. DOI:10.1097/CPM.0000000000000095
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    Bernard M Fischer · Judith A Voynow · Andrew J Ghio ·
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic illnesses in the world. The disease encompasses emphysema, chronic bronchitis, and small airway obstruction and can be caused by environmental exposures, primarily cigarette smoking. Since only a small subset of smokers develop COPD, it is believed that host factors interact with the environment to increase the propensity to develop disease. The major pathogenic factors causing disease include infection and inflammation, protease and antiprotease imbalance, and oxidative stress overwhelming antioxidant defenses. In this review, we will discuss the major environmental and host sources for oxidative stress; discuss how oxidative stress regulates chronic bronchitis; review the latest information on genetic predisposition to COPD, specifically focusing on oxidant/antioxidant imbalance; and review future antioxidant therapeutic options for COPD. The complexity of COPD will necessitate a multi-target therapeutic approach. It is likely that antioxidant supplementation and dietary antioxidants will have a place in these future combination therapies.
    International Journal of COPD 02/2015; 10:261. DOI:10.2147/COPD.S42414 · 3.14 Impact Factor
  • Judith A. Voynow · Alison J. Montpetit ·
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    ABSTRACT: This editorial summarizes the challenges of exhaled breath biomarker research particularly for nasal NO. We also introduce a new focus for Pediatric Pulmonology, a section on Translational Medicine. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.
    Pediatric Pulmonology 01/2015; 50(1). DOI:10.1002/ppul.23111 · 2.70 Impact Factor

  • Journal of Allergy and Clinical Immunology 09/2014; 135(2). DOI:10.1016/j.jaci.2014.07.058 · 11.48 Impact Factor
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    ABSTRACT: Diacetyl (DA), a component of artificial butter flavoring, has been linked to the development of bronchiolitis obliterans (BO), a disease of airway epithelial injury and airway fibrosis. The epidermal growth factor receptor (EGFR) ligand, amphiregulin (AREG), has been implicated in other types of epithelial injury and lung fibrosis. We investigated the effects of DA directly on the pulmonary epithelium and we hypothesized that DA exposure would result in epithelial cell shedding of AREG. Consistent with this hypothesis, we demonstrate that DA increases AREG by the pulmonary epithelial cell line NCI-H292 and by multiple independent primary human airway epithelial donors grown under physiologically relevant conditions at the air-liquid interface (ALI). Furthermore, we demonstrate that AREG shedding occurs through a tumor necrosis factor-alpha converting enzyme (TACE)-dependent mechanism via inhibition of TACE activity in epithelial cells using the small molecule inhibitor, TAPI-1, as well as TACE specific siRNA. Finally, we demonstrate supportive in vivo results showing increase AREG transcript and protein levels in the lungs of rodents with DA-induced BO. In summary, our novel in vitro and in vivo observations suggest further study of AREG is warranted in the pathogenesis of DA-induced BO.
    American Journal of Respiratory Cell and Molecular Biology 05/2014; 51(4). DOI:10.1165/rcmb.2013-0339OC · 3.99 Impact Factor
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    ABSTRACT: Neutrophil elastase (NE) is a major inflammatory mediator in cystic fibrosis (CF) that is a robust predictor of lung disease progression. NE directly causes airway injury via protease activity, and propagates persistent neutrophilic inflammation by upregulation of neutrophil chemokine expression. Despite its key role in the pathogenesis of CF lung disease, there are currently no effective anti-protease therapies available to CF patients. Although heparin is an effective anti-protease and anti-inflammatory agent, its anti-coagulant activity prohibits its use in CF due to risk of pulmonary hemorrhage. In this report, we demonstrate the efficacy of a 2-O, 3-O- desulfated heparin (ODSH), a modified heparin with minimal anti-coagulant activity, to inhibit NE activity and to block NE-induced airway inflammation. Using an established murine model of intratracheal NE-induced airway inflammation, we tested the efficacy of intratracheal ODSH to block NE-generated neutrophil chemoattractants and NE-triggered airway neutrophilic inflammation. ODSH inhibited NE-induced keratinocyte-derived chemoattractant (KC) and high mobility group box 1 (HMGB1) release in bronchoalveolar lavage (BAL). ODSH also blocked NE-stimulated HMGB1 release from murine macrophages in vitro and inhibited NE activity in functional assays consistent with prior reports of anti-protease activity. In summary, this report suggests that ODSH is a promising anti-protease and anti-inflammatory agent that may be useful as an airway therapy in CF.
    American Journal of Respiratory Cell and Molecular Biology 12/2013; 50(4). DOI:10.1165/rcmb.2013-0338RC · 3.99 Impact Factor
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    ABSTRACT: Despite modern sequencing efforts, the difficulty in assembly of highly repetitive sequence has prevented resolution of human genome gaps, including some in the coding regions of genes with important biological functions. One such gene, MUC5AC, encodes a large, secreted mucin, which is one of the two major secreted mucins in human airways. Currently, the MUC5AC region contains a gap in the human genome reference (hg19) across the large, highly repetitive and complex central exon. This exon region is predicted to contain imperfect tandem repeat sequences and multiple conserved cysteine-rich (CysD) domains. To resolve the MUC5AC genomic gap, we utilized high-fidelity, long polymerase chain reaction, followed by Pacific Biosciences' single molecule real time (SMRT®) sequencing. This technology yielded long sequence reads and robust coverage that allowed for de novo sequence assembly spanning the entire repetitive region. Furthermore, we used SMRT Sequencing of PCR amplicons covering the central exon to identify genetic variation in four individuals. The results demonstrated the presence of segmental duplications of CysD domains, insertions/deletions (indels) of tandem repeats, and single nucleotide variants. Additional studies demonstrated that one of the identified tandem repeat insertions is tagged by non-exonic single nucleotide polymorphisms. Taken together, these data illustrate the successful utility of SMRT Sequencing long reads for de novo assembly of large repetitive sequences to fill the gaps in the human genome. Characterization of the MUC5AC gene and the sequence variation in the central exon will facilitate genetic and functional studies for this critical airway mucin.
    American Journal of Respiratory Cell and Molecular Biology 09/2013; 50(1). DOI:10.1165/rcmb.2013-0235OC · 3.99 Impact Factor
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    ABSTRACT: This is the first published report of a young girl with co-inherited sickle cell-beta+ thalassemia and cystic fibrosis. Although a small subset of patients with co-inherited cystic fibrosis and other hemoglobinopathies have been reported, this patient developed early hematologic and pulmonary complications that were more severe than the previous cases. To assess pulmonary co-morbidities, we used infant pulmonary function testing through the raised volume rapid thoracoabdominal compression technique as both an established study of early cystic fibrosis and also as a newer study of mechanism for early sickle cell lung disease. This further serves as the first report of the raised volume rapid thoracoabdominal compression technique to determine raised volume forced expiratory flows and fractional lung volumes in a patient with a hemoglobinopathy. A 2-year-old African-American girl with co-inherited cystic fibrosis and sickle cell-beta+ thalassemia developed severe hematologic complications (recurrent vaso-occlusive events, hepatic sequestration, and acute chest syndrome) during periods of cystic fibrosis pulmonary exacerbations and weight loss. Because cystic fibrosis and sickle cell-beta+ thalassemia both confer distinct patterns of pulmonary disease, infant pulmonary function testing with the raised volume rapid thoracoabdominal compression technique was used to define respiratory pathophysiology and guide treatment options. Infant pulmonary function testing data demonstrated moderate-to-severe lower airways obstruction, moderate air trapping, and no evidence of restrictive lung disease. Infant pulmonary function testing with the raised volume rapid thoracoabdominal compression technique guided therapy in this patient with cystic fibrosis and sickle cell-beta+ thalassemia. Although this is an original case report on a unique patient, this case highlights the need to evaluate early respiratory pathophysiology in a broader population of young patients with hemoglobinopathies and screen those at risk for early pulmonary co-morbidities.
    Journal of Medical Case Reports 07/2013; 7(1):203. DOI:10.1186/1752-1947-7-203

  • Paediatric respiratory reviews 07/2013; 14:S71-S72. DOI:10.1016/S1526-0542(13)70114-3 · 2.20 Impact Factor
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    ABSTRACT: Neutrophilic inflammation is associated with chronic airway diseases. It has been observed that human neutrophil elastase (HNE), which is secreted by active neutrophils during inflammation, induces both mucin overproduction and goblet cell metaplasia. Several in vitro studies suggest that tumor necrosis factor-α converting enzyme (TACE) regulates the signaling axis that mediates HNE-induced mucin overproduction; however, it is unknown whether TACE performs a similar function in HNE-induced goblet cell metaplasia in vivo. We conducted this study to determine if the inactivation of Tace gene expression attenuates HNE-induced goblet cell metaplasia in mice. Deletion of Tace is lethal shortly after birth in mice; therefore, we utilized Tace(flox/flox) R26Cre(+/-) ER mice and induced a conditional deletion of Tace using a tamoxifen injection. Wild-type mice were given tamoxifen to control for its effect. Tace conditional deletion mice and wild-type mice were exposed to HNE via nasal instillation three times at three-day intervals and the lungs were harvested on day 11 after initial HNE exposure. Using Periodic acid-Schiff staining and MUC5AC immunohistochemical staining to visualize goblet cells in the lungs, we found that HNE induced goblet cell metaplasia in the wild-type mice and that HNE-induced goblet cell metaplasia was significantly attenuated in the Tace conditional deletion mice. These findings suggest that TACE could be a potential target in the treatment of goblet cell metaplasia in patients with chronic airway diseases.
    AJP Lung Cellular and Molecular Physiology 04/2013; 304(10). DOI:10.1152/ajplung.00259.2012 · 4.08 Impact Factor
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    ABSTRACT: There is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals) were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP). Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES). Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative) relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively) with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.
    International Journal of COPD 01/2013; 8:45-51. DOI:10.2147/COPD.S37897 · 3.14 Impact Factor
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    ABSTRACT: Cystic Fibrosis (CF) is a chronic lung disease characterized by chronic neutrophilic airway inflammation and increased levels of neutrophil elastase (NE) in the airways. We have previously reported that NE treatment triggers cell cycle arrest. Cell cycle arrest can lead to senescence, a complete loss of replicative capacity. Importantly, senescent cells can be pro-inflammatory and would perpetuate CF chronic inflammation. By immunohistochemistry, we evaluated whether airway sections from CF and control subjects expressed markers of senescence, including: p16(INK4a) (p16), a cyclin dependent kinase inhibitor, phospho-Histone H2A.X (γH2A.X) and phospho-checkpoint 2 kinase (phospho-Chk2), which are also DNA damage response markers. Compared to airway epithelium from control subjects, CF airway epithelium had increased levels of expression of all three senescence markers. We hypothesized that the high load of NE in the CF airway triggers epithelial senescence by upregulating expression of p16, which inhibits cyclin dependent kinase 4 (CDK4). Normal human bronchial epithelial (NHBE) cells, cultured in air-liquid interface were treated with NE (0, 200 and 500 nM) to induce visible injury. Total cell lysates were collected and evaluated by Western analysis for p16 protein expression and CDK4 kinase activity. NE significantly increased p16 expression and decreased CDK4 kinase activity in NHBE cells. These results support the concept that NE triggers expression of senescence markers in CF airway epithelial cells.
    AJP Lung Cellular and Molecular Physiology 01/2013; 304(6). DOI:10.1152/ajplung.00091.2012 · 4.08 Impact Factor
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    ABSTRACT: NADPH quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1, as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. Yet, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1, ozone exposure results in increased generation of A2-isoprostane, a cyclopentenone isoprostane that blunts inflammation. Using GC/MS, we found that NQO1-null mice had greater lung tissue levels of D2- and E2-isoprostanes, the precursors of J2-, A2-isoprostanes, both at baseline and following ozone exposure compared to congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells, that A2-isoprostane inhibited ozone-induced NF-kB activation and IL-8 regulation. Furthermore, we determined that A2-isoprostane covalently modified the active Cys179 domain in Inhibitory kB Kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A2-isoprostane inhibition of NF-kB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A2-isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.
    Journal of Biological Chemistry 12/2012; 288(7). DOI:10.1074/jbc.M112.438440 · 4.57 Impact Factor
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    ABSTRACT: Mucous cell metaplasia (MCM) and neutrophil-predominant airway inflammation are pathological features of chronic inflammatory airway diseases. A signature feature of MCM is increased expression of a major respiratory tract mucin, MUC5AC. Neutrophil elastase (NE) upregulates MUC5AC in primary airway epithelial cells by generating reactive oxygen species, and this response is due in part to upregulation of NADPH quinone oxidoreductase 1 (NQO1) activity. Delivery of NE directly to the airway triggers inflammation and MCM and increases synthesis and secretion of MUC5AC protein from airway epithelial cells. We hypothesized that NE-induced MCM is mediated in vivo by NQO1. Male wild-type and Nqo1-null mice (C57BL/6 background) were exposed to human NE (50 μg) or vehicle via oropharyngeal aspiration on days 1, 4, and 7. On days 8 and 11, lung tissues and bronchoalveolar lavage (BAL) samples were obtained and evaluated for MCM, inflammation, and oxidative stress. MCM, inflammation, and production of specific cytokines, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-2, interleukin-4, and interleukin-5 were diminished in NE-treated Nqo1-null mice compared with NE-treated wild-type mice. However, in contrast to the role of NQO1 in vitro, we demonstrate that NE-treated Nqo1-null mice had greater levels of BAL and lung tissue lipid carbonyls and greater BAL iron on day 11, all consistent with increased oxidative stress. NQO1 is required for NE-induced inflammation and MCM. This model system demonstrates that NE-induced MCM directly correlates with inflammation, but not with oxidative stress.
    AJP Lung Cellular and Molecular Physiology 06/2012; 303(3):L181-8. DOI:10.1152/ajplung.00084.2012 · 4.08 Impact Factor

  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012

  • American Thoracic Society 2012 International Conference, May 18-23, 2012 • San Francisco, California; 05/2012
  • Source
    Bernard M Fischer · Elizabeth Pavlisko · Judith A Voynow ·
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    ABSTRACT: Patients with chronic obstructive pulmonary disease (COPD) exhibit dominant features of chronic bronchitis, emphysema, and/or asthma, with a common phenotype of airflow obstruction. COPD pulmonary physiology reflects the sum of pathological changes in COPD, which can occur in large central airways, small peripheral airways, and the lung parenchyma. Quantitative or high-resolution computed tomography is used as a surrogate measure for assessment of disease progression. Different biological or molecular markers have been reported that reflect the mechanistic or pathogenic triad of inflammation, proteases, and oxidants and correspond to the different aspects of COPD histopathology. Similar to the pathogenic triad markers, genetic variations or polymorphisms have also been linked to COPD-associated inflammation, protease-antiprotease imbalance, and oxidative stress. Furthermore, in recent years, there have been reports identifying aging-associated mechanistic markers as downstream consequences of the pathogenic triad in the lungs from COPD patients. For this review, the authors have limited their discussion to a review of mechanistic markers and genetic variations and their association with COPD histopathology and disease status.
    International Journal of COPD 08/2011; 6(1):413-21. DOI:10.2147/COPD.S10770 · 3.14 Impact Factor
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    ABSTRACT: Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia, diffuse pulmonary infiltrates and poor lung compliance in the absence of left heart failure1,2. Early pathogenic changes include pulmonary neutrophil sequestration and intravascular fibrin-platelet aggregates3,5. Subsequent injury to the alveolar-capillary barrier leads to increased pulmonary vascular permeability causing progressive lung inflammation and pulmonary edema4. Persistent inflammation frequently leads to fibrosis.
    07/2011: pages 187-195;
  • J. Voynow · M. Meyer · B. M. Fischer · E. Potts · W. M. Foster ·

    Paediatric respiratory reviews 06/2011; 12. DOI:10.1016/S1526-0542(11)70129-4 · 2.20 Impact Factor

Publication Stats

2k Citations
247.76 Total Impact Points


  • 2015
    • Virginia Commonwealth University
      • Department of Pediatrics
      Ричмонд, Virginia, United States
  • 1998-2014
    • Duke University Medical Center
      • • Department of Medicine
      • • Department of Pediatrics
      Durham, North Carolina, United States
    • George Washington University
      • Department of Pediatrics
      Washington, Washington, D.C., United States
  • 1998-2013
    • Duke University
      Durham, North Carolina, United States
  • 1999-2006
    • Children's National Medical Center
      • Center for Genetic Medicine Research
      Washington, D. C., DC, United States
    • North Carolina State University
      • College of Veterinary Medicine
      Raleigh, North Carolina, United States
  • 1988-1991
    • The Children's Hospital of Philadelphia
      • Department of Pediatrics
      Filadelfia, Pennsylvania, United States