Bruce K Rubin

Virginia Commonwealth University, Richmond, Virginia, United States

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Publications (174)644.33 Total impact

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    ABSTRACT: Objective There are some controversial reports that investigated the usefulness of exhaled nitric oxide (eNO) to predict the efficacy of inhaled corticosteroids (ICS) in chronic cough patients. Therefore, we retrospectively analyzed the usefulness of eNO measurement with portable analyzer to predict the requirement of ICS therapy in persistent cough (defined as lasting for 3 weeks or more) patients in Japan and investigated whether it might improve the management of persistent cough at primary care practice.Methods We retrospectively reviewed the clinical records of adult patients who had been referred to our hospital for persistent cough from June 1st, 2009 to April 30, 2011.Results42 patients had the requirement of ICS (Group S) and 35 patients had no requirement of ICS (Group N). 43% of the patients who required ICS had not received ICS and 29% of the patients who did not required ICS had received ICS. In the steroid-naive patients without current smoking, mean eNO level was significantly higher in Group S (60.6±14.1 ppb vs. 22.2±2.3 ppb, P=0.001) and the sensitivity and the specificity of eNO for predicting the requirement of ICS were 78.6 % and 80.0 % respectively. The rate of the patients who received inappropriate treatment about ICS tended to be reduced from 41% to 21% if the eNO was used to predict the requirement of ICS with cut-off value of eNO 26.5 ppb (P=0.118).Conclusions Measurement of eNO could be one of the management tools for persistent cough at primary care practice.
    The Clinical Respiratory Journal 10/2014; · 1.66 Impact Factor
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    ABSTRACT: The term bronchial hyperresponsiveness is generally used to describe a heightened airway smooth muscle bronchoconstrictor response measured by bronchoprovocation testing. However, the airway also responds to inflammation or bronchoprovocation with increased mucus secretion. We use the term "secretory hyperresponsiveness" to mean increased mucus secretion either intrinsically or in response to bronchoprovocation. This is not the same as retained phlegm or sputum. Unlike smooth muscle contraction, which is rapidly reversible using a bronchodilator, mucus hypersecretion produces airflow limitation that reverses more slowly and depends upon secretion clearance from the airway. Certain groups of patients appear to have greater mucus secretory response, including those with middle lobe syndrome, cough-dominant ("cough-variant") asthma, and severe asthma. Secretory hyperresponsiveness also is a component of forms of lung cancer associated with bronchorrhea. An extreme form of secretory hyperresponsiveness may lead to plastic bronchitis, a disease characterized by rigid branching mucus casts that obstruct the airway. Secretory hyperresponsiveness and mucus hypersecretion appear to be related to activation of the extracellular-regulated kinase 1/2, signaling through the epidermal growth factor receptor, or secretory phospholipases A2. Recognizing secretory hyperresponsiveness as a distinct clinical entity may lead to more effective and targeted therapy for these diseases.
    Chest 08/2014; 146(2):496-507. · 7.13 Impact Factor
  • Bruce K Rubin, Ronald W Williams
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    ABSTRACT: Patients with tracheostomies, those requiring mechanical ventilation, and those too small or compromised for conventional devices, are realizing the benefits of increasingly sophisticated aerosol delivery systems. New medicines and novel aerosol formulations, have enhanced our ability to treat lung disease, and are opening the doors for therapy to treat diseases like diabetes, pulmonary hypertension, and cancer. Progress in the aerosol delivery of drugs has been spurred by the significant benefits, including ease of use, patient comfort, greater selectivity of effect, and the potential to decrease side effects.
    Advanced drug delivery reviews. 06/2014;
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    ABSTRACT: Bacterial lipopolysaccharide (LPS) and interleukin (IL)-13 increase mucus secretion and inflammatory cytokine production in normal human bronchial epithelial (NHBE) cells. We evaluated the effect of club cell 10-kDa protein (CC10), an anti-inflammatory protein produced by epithelial cells, on mucus secretion, cell morphology and inflammatory cytokine production. NHBE cells were cultured at an air-liquid interface with CC10 or vehicle and exposed to LPS on day 14. Mucin MUC5AC, IL-8 and granulocyte-macrophage colony-stimulating factor were measured in cell supernatants. MUC5AC and IL-8 mRNA expression were measured by real-time PCR. Western blotting was used to evaluate nuclear factor (NF)-κB and extracellular signal-regulated kinase (ERK) activation. Cells were evaluated histologically. Additionally, NHBE cells were exposed to IL-13 and CC10 for 14 days, and secretion of the mucins MUC5AC and MUC5B was measured. MUC5AC secretion stimulated either by LPS or by IL-13 was attenuated by CC10 at 20 ng·mL(-1) (p<0.05). CC10 at 20 ng·mL(-1) also attenuated IL-8 secretion (p<0.05). MUC5AC and IL-8 mRNA expression were also decreased by CC10 (p<0.05). CC10 attenuated phosphorylation of NF-κB (p<0.05) and ERK1/2 (p<0.05). CC10 attenuates LPS-induced mucus secretion in airway cells, in part due to inhibition of NF-κB and ERK phosphorylation.
    European Respiratory Journal 05/2014; · 6.36 Impact Factor
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    ABSTRACT: IL-13, a helper T-cell type2 (Th2) cytokine transforms cultured airway epithelial cells to goblet cells and this is not inhibited by corticosteroids. IL-33 stimulates Th2 cytokines and is highly expressed in airways of persons with asthma. The effect of IL-33 on goblet cell differentiation and cytokine secretion has not been described. We examined the effect of IL-33 on CXCL8/IL-8 secretion from goblet or normally differentiated human bronchial epithelial (NHBE) cells and signaling pathways associated with IL-33 activation in these cells. NHBE cells were grown to goblet or normally differentiated ciliated cell phenotype at air-liquid interface in the presence or absence of IL-13. After 14 days, differentiated cells were exposed to IL-33 for 24 hours. CXCL8/IL-8 secretion into the apical (air) side of the goblet cells was greater than from normally differentiated cells (p<0.01) and IL-33 stimulated apical CXCL8/IL-8 release from goblet cells but not from normally differentiated cells (p<0.01). IL-33 increased ERK 1/2 phosphorylation in goblet cells (p<0.05) and PD98059, a MAPK/ERK kinase inhibitor attenuated IL-33 stimulated CXCL8/IL-8 secretion from goblet cells (p<0.001). IL-13 induced ST2 mRNA (p<0.02) and membrane bound ST2 protein expression on the apical side surface of goblet cells compared with normally differentiated cells, and neutralization with anti-ST2R antibody attenuated IL-33-induced apical CXCL8/IL-8 secretion from goblet cells (p<0.02). Goblet cells secrete CXCL8/IL-8 and this is increased by IL-33 through ST2R-ERK pathway suggesting a mechanism for enhanced airway inflammation in the asthmatic airway with goblet cell metaplasia. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Allergy 01/2014; · 4.79 Impact Factor
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    ABSTRACT: Smoking is responsible for most chronic obstructive pulmonary disease (COPD). Although persons with COPD often have concomitant nasal disease, there are few studies that report physiological or inflammatory changes in the upper airways in young asymptomatic smokers. We investigated physiologic and inflammatory changes in the nasal and lower airways of young smokers and if these changes were related to smoking history. Seventy-two subjects aged between 18 and 35 years (32 healthy nonsmokers and 40 young smokers) participated in this study. We measured nasal mucociliary clearance (MCC), nasal mucus surface contact angle, cell counts, myeloperoxidase and cytokine concentrations in nasal lavage fluid, exhaled breath condensate (EBC) pH and lung function. Smokers had faster MCC, increased number of cells (macrophages, ciliated and goblet cells), increased lavage myeloperoxidase and decreased EBC pH compared with nonsmokers. There was a significant inverse relationship between pack-year smoking history and EBC pH. There were no differences in lung function or mucus surface properties comparing smokers to nonsmokers. Young adult smokers have functional and inflammatory changes in the nasal and lower airways and these correlate with smoking history. However, in these young smokers, smoking history was not associated with pulmonary function decline, probably because it is unlikely that spirometry detects early physiologic changes in the airways.
    Chest 12/2013; · 7.13 Impact Factor
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    ABSTRACT: Airway clearance therapy (ACT) is used in a variety of settings for a variety of ailments. These guidelines were developed from a systematic review with the purpose of determining whether the use of nonpharmacologic ACT improves oxygenation, reduces length of time on the ventilator, reduces length of stay in the intensive care unit (ICU), resolves atelectasis/consolidation, and/or improves respiratory mechanics vs. usual care in 3 populations. For hospitalized, adult and pediatric patients without cystic fibrosis, 1) chest physiotherapy (CPT) is not recommended for the routine treatment of uncomplicated pneumonia; 2) ACT is not recommended for routine use in patients with COPD; 3) ACT may be considered in patients with COPD with symptomatic secretion retention, guided by patient preference, toleration, and effectiveness of therapy; 4) ACT is not recommended if the patient is able to mobilize secretions with cough, but instruction in effective cough technique may be useful. For adult and pediatric patients with neuromuscular disease, respiratory muscle weakness, or impaired cough, 1) cough assist techniques should be used in patients with neuromuscular disease, particularly when peak cough flow is < 270 L/min; CPT, positive expiratory pressure, intrapulmonary percussive ventilation, and high frequency chest wall compression cannot be recommended due to insufficient evidence. For post-operative adult and pediatric patients, 1) incentive spirometry is not recommended for routine, prophylactic use in post-operative patients, 2) early mobility and ambulation is recommended to reduce post-operative complications and promote airway clearance, 3) ACT is not recommended for routine post-operative care. The lack of available high level evidence related to ACT should prompt the design and completion of properly designed studies to determine the appropriate role for these therapies.
    Respiratory care. 11/2013;
  • Bruce K Rubin
    American Journal of Respiratory and Critical Care Medicine 09/2013; 188(6):634-5. · 11.04 Impact Factor
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    ABSTRACT: Guaifenesin (GGE) has been studied as a cough suppressant and as an expectorant; however published studies to date have failed to find a consistent benefit. An 8-day, multi-center, clinical trial conducted to study the effect of two 600 mg extended-release GGE tablets twice daily for 1 week, on old symptoms,sputum volume and properties in adolescents and adults with productive cough from an acute respiratory tract infection (RTI). The study enrolled 378 subjects (GGE n=188, placebo n=190) who were otherwise healthy and had an RTI for up to 5 days before enrollment. Subjects suffered from at least two of three symptoms of cough, thickened mucus, and chest congestion. A total of 151 GGE and 144 control subjects completed the full protocol. Single sputum samples were collected from each subject on days 1, 3, 4 and 8 of the study. The rheology and interfacial tension of sputum was measured and 24 hour collected samples from days 1 and 4 were analyzed for total volume and hydration. Symptoms in both the guaifenesin and placebo groups improved to a similar degree over time. There were no significant differences between the GGE and placebo groups for sputum volume (p = 0.408), percent solids (p = 0.694), interfacial tension (p = 0.881), elasticity (p = 0.710), viscosity (p = 0.447), or mechanical impedance ( p = 0.749). The recommended dosage of GGE had no measurable effect on sputum volume or properties and is unlikely to be an expectorant or mucolytic when used to treat acute RTI. clinicaltrials.gov NCT01046136.
    Respiratory care. 09/2013;
  • Bruce K Rubin, Naomi Kondo Nakagawa
    Respiratory care. 09/2013; 58(9):e117-8.
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    ABSTRACT: The adolescent with asthma experiences a period of physical and psychosocial changes that affect their health and well-being. Overall, adolescents with asthma are at increased risk for asthma morbidity and death. Increased rates of depression and anxiety, for the adolescent and their caregivers, can lead to non-adherence to their medical regimens, poor symptom control, and poor treatment outcomes. Contextual factors, such as race, ethnicity, and living situation, affect the prevalence, morbidity, and mortality for the adolescent with asthma. These factors also affect the transition process for adolescents entering adult medical care. An overview is presented of how the adolescent with asthma differs and how healthcare providers can promote effective asthma management and better asthma control.
    Paediatric Respiratory Reviews 08/2013; · 2.77 Impact Factor
  • Bart L Rottier, Bruce K Rubin
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    ABSTRACT: Asthma is usually treated with inhaled corticosteroids (ICS) and bronchodilators generated from pressurized metered dose inhalers (pMDI), dry powder inhalers (DPI), or nebulizers. The target areas for ICS and beta 2-agonists in the treatment of asthma are explained. Drug deposition not only depends on particle size, but also on inhalation manoeuvre. Myths regarding inhalation treatments lead to less than optimal use of these delivery systems. We discuss the origin of many of these myths and provide the background and evidence for rejecting them.
    Paediatric Respiratory Reviews 03/2013; · 2.77 Impact Factor
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    ABSTRACT: Primary ciliary dyskinesia (PCD), resulting from defects in cilia assembly or motility, is caused by mutations in a number of genes encoding axonemal proteins. PCD phenotypes are variable, and include recurrent respiratory tract infections, bronchiectasis, hydrocephaly, situs inversus and male infertility. We generated knockout mice for the Spag17 gene, which encodes a central pair (CP) protein present in the axonemes of cells with "9+2" motile cilia or flagella. Targeting of Spag17 resulted in a severe phenotype characterized by immotile nasal and tracheal cilia, reduced clearance of nasal mucus, profound respiratory distress associated with lung fluid accumulation and disruption of the alveolar epithelium, cerebral ventricular expansion consistent with emerging hydrocephalus, failure to suckle, and neonatal demise within 12 h of birth. Ultrastructural analysis revealed loss of one CP microtubule in approximately one quarter of tracheal cilia axonemes, absence of a C1 microtubule projection, as well as less frequent CP structural abnormalities. SPAG6 and SPAG16, CP proteins that interact with SPAG17, were increased in tracheal tissue from SPAG17-deficient mice. We conclude that Spag17 plays a critical role in the function and structure of motile cilia, and that the neonatal lethality is likely explained by impaired airway mucociliary clearance.
    American Journal of Respiratory Cell and Molecular Biology 02/2013; · 4.15 Impact Factor
  • Evangelia Daviskas, Bruce K Rubin
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    ABSTRACT: Insufficient hydration at the airway surface can make mucus adherent and poorly cleared. Cough, the major mechanism of mucus clearance in disease, is ineffective when mucus is adhesive. Inhaled mannitol creates an osmotic drive for water to move into the airway lumen. The consequent increased hydration of the airway surface decreases the adherence of mucus to the epithelium, facilitates the coupling of mucus and cilia thereby increasing mucus clearance. Inhaled mannitol also promotes effective coughing and stimulates mucociliary clearance. The beneficial effect of mannitol on mucus and its clearance has been demonstrated in patients with asthma, bronchiectasis and cystic fibrosis. Inhaled dry powder mannitol (Bronchitol™) is promising to be an effective treatment for the clearance of retained airway secretions.
    Expert Review of Respiratory Medicine 02/2013; 7(1):65-75.
  • Bruce K. Rubin
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    ABSTRACT: As a student I recall being told that half of what we would learn in medical school would be proven to be wrong. The challenges were to identify the incorrect half and, often more challenging, be willing to give up our entrenched ideas. Myths have been defined as traditional concepts or practice with no basis in fact. A misunderstanding is a mistaken approach or incomplete knowledge that can be resolved with better evidence, while firmly established misunderstandings can become dogma; a point of view put forth as authoritative without basis in fact. In this paper, I explore a number of myths, mistakes, and dogma related to cystic fibrosis disease and care. Many of these are myths that have long been vanquished and even forgotten, while others are controversial. In the future, many things taken as either fact or “clinical experience” today will be proven wrong. Let us examine these myths with an open mind and willingness to change our beliefs when justified.
    Paediatric Respiratory Reviews 01/2013; · 2.77 Impact Factor
  • Bruce K Rubin, Randall Cohen, Kelley M Dodson
    International journal of pediatric otorhinolaryngology 12/2012; · 0.85 Impact Factor
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    ABSTRACT: BACKGROUND: Some investigation revealed the association between depression and physical measurements of chronic obstructive pulmonary disease (COPD) patients in North America and Europe but limited studies in Asia were performed. METHODS: In this cross-sectional study, consecutive 84 stable outpatients with COPD (Age: 72.0 ± 9.0. Forced expiratory volume in one second (%predicted) 46 ± 15%. Fifteen females (17.9%)) in a Japanese community based hospital were recruited. "Probable depression" was defined as short form of the geriatric depression scale (SF-GDS) ≥ 6. Relationships among commonly used physical measurements, SF-GDS raw score, and probable depression were evaluated with Spearman's rank correlation test, multiple linear regression analysis, logistic regression analysis, and receiver operating characteristic curve. RESULTS: Thirty two (38.1%) had probable depression. Body mass index, obstruction, dyspnea, exercise capacity index; forced expiratory volume in one second (%predicted); modified medical research council dyspnea scale; six-minute walk distance; saturation of oxygen on artery by pulse oximetry had followings: (i) simple correlations (|r|:0.42 0.60 , P < .001 for all) for SF GDS raw score, (ii) partial correlations (|r|:0.25 0.51 , P < .05 for all) for SF GDS raw score after adjusting demographic and social factors, (iii) association for probable depression in logistic regression analysis after adjusting demographic and social factors (P < .05 for all), and (iv) area under the receiver operating characteristic curves for probable depression (area under the curves: 0.719-0.841, P < .001 for any), CONCLUSIONS: Physical parameters were associated with depression in our Japanese COPD outpatients.
    Respiratory care 12/2012; · 2.03 Impact Factor
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    ABSTRACT: Cardiac asthma has been defined as wheezing, coughing and orthopnea due to congestive heart failure. The clinical distinction between bronchial asthma and cardiac asthma can be straight forward, except in patients with chronic lung disease coexisting with left heart disease. Pulmonary edema and pulmonary vascular congestion have been thought to be the primary causes of cardiac asthma but most patients have a poor response to diuretics. There appears to be limited effectiveness of classical asthma medications like bronchodilators or corticosteroids in treating cardiac asthma. Evidence suggests that circulating inflammatory factors and tissue growth factors also lead to airway obstruction suggesting the possibility of developing novel therapies.
    Expert Review of Respiratory Medicine 12/2012; 6(6):705-14.
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    ABSTRACT: ABSTRACT BACKGROUND: We have previously shown that nasal mucociliary clearance is decreased in critically ill elderly subjects; most of whom had diabetes (DM) and/or hypertension (HTN). To determine if these changes were due to the effects of aging, disease, or critical illness, we studied nasal mucociliary clearance and mucus properties in an ambulatory population consisting of young and elderly, healthy and DM and/or HTN. METHODS: Of 440 subjects contacted, 252 entered the study. The subjects were divided into (a) healthy (n=79, 18-94 yrs, 50 male) and (b) DM and/or HTN, of which 37 had DM (14-90 yrs, 12 male), 52 had HTN (23-90 yrs, 12 male) and 84 had both DM and HTN (25-82 yrs, 33 male). Subjects were also grouped by age: <40 yrs, 40-59 yrs, and ≥60 yrs. We assessed demographic and clinical data, quality of life using the Short-Form (SF)-36 questionnaire, nasal mucociliary clearance using the saccharine transit test (STT) and in vitro mucus properties by examining the sneeze (high air flow) clearability and contact angle. A logistic regression analysis for prolonged STT > 12 minutes was used controlled for age, sex, and diseases. RESULTS: Subjects over 60 yrs reported decreased SF-36 physical component relative to other age groups. Sex, body mass index, blood pressure, heart rate, pulse oximetry, blood glucose level and mucus properties were not associated with prolonged STT. Aging and DM and/or HTN independently increased the risk of prolonged STT. CONCLUSIONS: Aging, DM, HTN or both diseases are independently associated with decreased nasal mucociliary clearance. This may predispose toward respiratory infections.
    Chest 10/2012; · 7.13 Impact Factor
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    ABSTRACT: OBJECTIVE: Persistent otitis media with effusion is caused by poor clearance of middle ear fluid usually following an episode of acute otitis media. This fluid is thought to be viscous and poorly transportable by cilia. Because a subset of children require multiple myringotomy and tube placements for recurrent disease, we hypothesized that children requiring repeated procedures would have effusion fluid that was more viscous and less transportable than those having their first procedure. DESIGN: Prospective clinical study. SETTING: Tertiary care center. PATIENTS AND INTERVENTIONS: Middle ear secretions were collected at the time of myringotomy and tube insertion in 36 children accrued sequentially. Twenty-six of these children were having their first procedure and 10 had previously undergone myringotomy and tube placement. MAIN OUTCOME MEASURES: The secretions were evaluated for in vitro mucociliary transportability, and dynamic rheology in a magnetic microrheometer. RESULTS: Children with the need for repeated procedures had effusions with lower mucociliary transportability, and overall higher mean measures of surface mechanical impedance/frictional adhesion, but these did not reach statistical significance. Mucopurulent effusions had significantly greater transportability than both the mucoid and serous effusions in both groups. CONCLUSIONS: Persistent or recurrent otitis media with effusion is associated with poorly transportable middle ear fluid, which may have higher frictional adhesion. The best mucociliary transportability was measured in mucopurulent effusions.
    International journal of pediatric otorhinolaryngology 09/2012; · 0.85 Impact Factor

Publication Stats

2k Citations
644.33 Total Impact Points

Institutions

  • 2009–2014
    • Virginia Commonwealth University
      • Department of Pediatrics
      Richmond, Virginia, United States
    • Nemours
      Jacksonville, Florida, United States
  • 2008–2014
    • Children's Hospital of Richmond
      Richmond, Virginia, United States
    • GlaxoSmithKline plc.
      Londinium, England, United Kingdom
    • Texas Children's Hospital
      Houston, Texas, United States
    • Seattle Children's Hospital
      • Children's Hospital and Regional Medical Center
      Seattle, Washington, United States
  • 2005–2013
    • Royal Prince Alfred Hospital
      Camperdown, New South Wales, Australia
    • University of North Carolina at Chapel Hill
      • Department of Pediatrics
      Chapel Hill, NC, United States
  • 1999–2013
    • University of Groningen
      • Groningen Research Institute for Asthma and COPD (GRIAC)
      Groningen, Province of Groningen, Netherlands
    • Mie University
      Tu, Mie, Japan
  • 2012
    • The Royal Children's Hospital
      • Department of Respiratory Medicine
      Melbourne, Victoria, Australia
  • 2004–2011
    • Philipps University of Marburg
      Marburg, Hesse, Germany
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 1976–2010
    • Wake Forest School of Medicine
      • • Department of Biomedical Engineering
      • • Department of Pediatrics
      Winston-Salem, North Carolina, United States
  • 2007–2009
    • Duke University Medical Center
      • Department of Pediatrics
      Durham, NC, United States
  • 2007–2008
    • Kyungpook National University
      • Department of Otolaryngology
      Daikyū, Daegu, South Korea
  • 2006
    • University of California, San Diego
      San Diego, California, United States
  • 2003–2006
    • Wake Forest University
      • Center for Integrative Medicine
      Winston-Salem, North Carolina, United States
  • 1995–2003
    • Washington University in St. Louis
      • Department of Pediatrics
      Saint Louis, MO, United States
  • 1990–2003
    • University of Alberta
      • Department of Pediatrics
      Edmonton, Alberta, Canada
  • 2001
    • University of North Carolina at Greensboro
      Greensboro, North Carolina, United States
  • 1997–2001
    • Saint Louis University
      • Department of Pediatrics
      Saint Louis, Michigan, United States
  • 1996–1998
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States
  • 1994
    • Brigham and Women's Hospital
      • Center for Brain Mind Medicine
      Boston, MA, United States