Zuzana Diamant

Baylor College of Medicine, Houston, Texas, United States

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Publications (91)340.3 Total impact

  • Zuzana Diamant · Nicola A Hanania

    No preview · Article · Nov 2015 · Current opinion in pulmonary medicine
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    ABSTRACT: Purpose of review: In humans, mast cells are ubiquitously present in tissues adjacent to external environment and consequently have an important sentential role in host defence, homeostasis and repair. Their key role in allergen-mediated conditions has been recognized for many decades already. So far, therapies targeting mast cells offered clinical efficacy in allergic conditions except for asthma. More recently, sophisticated sampling and detection techniques revealed pleiotrophic immunological and functional properties of mast cells in and beyond asthma with potential clinical and management implications. These findings bring back the mast cell as a key player in the field of asthma and warrant a review of the recent literature. Recent findings: The heterogeneity of human mast cells has been recognized: MCTC expressing both tryptase and chymase and MCT expressing tryptase only. Apart from this subphenotyping, mast cells may comprise and produce several other mediators and cytokines. Their immunological and functional properties depend on their (co)localization within the human body and can alter under changing conditions (e.g. pathogens, allergens, etc). Recent data revealed a novel mast cell phenotype within the alveolar tissue of patients with asthma. Increasing evidence shows a key role for alveolar mast cells in the pathophysiology of viral respiratory infections and in the development of allergen sensitization and asthma. Summary: Increasing evidence points toward a key role of mast cells in the pathophysiology and pathogenesis of asthma and this warrants further investigation and the development of effective targeted therapies.
    No preview · Article · Nov 2015 · Current opinion in pulmonary medicine
  • Amit D Parulekar · Zuzana Diamant · Nicola A Hanania
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    ABSTRACT: Purpose of review: Severe asthma is a heterogeneous syndrome. Classification of asthma into phenotypes and endotypes can improve understanding and treatment of the disease. Identification and utilization of biomarkers, particularly those linked to T2 inflammation, can help group patients into phenotypes, predict those who will respond to a specific therapy, and assess the response to treatment. Recent findings: Biomarkers are present in sputum, exhaled breath, and blood of patients with asthma. These include sputum eosinophils and neutrophils, fractional excretion of nitric oxide, blood eosinophilia, IgE, and periostin. Many of these biomarkers are associated with eosinophilic inflammation propagated mainly by T2 cytokines such as IL-5 and IL-13, which are released from Th2 cells and Type 2 innate lymphoid cells. Biomarkers have been utilized in recent trials of novel biologic agents targeted at T2 inflammation and may contribute to the defining population who would respond to these therapies. Summary: Despite advances in the identification and utilization of asthma biomarkers, further studies are needed to better clarify the role of biomarkers, individually or in combination, in the diagnosis and treatment of severe asthma. Future therapeutic trials should include the use of biomarkers in their design, which may lead to a more personalized approach to therapy and improved outcomes.
    No preview · Article · Nov 2015 · Current opinion in pulmonary medicine
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    ABSTRACT: Rationale: Exercise-induced bronchoconstriction (EIB) can be prevented by a single dose of montelukast (MLK). The effect is variable, similar to the variable responsiveness observed after daily treatment with MLK. We hypothesized that the effect of a single MLK-dose (5 or 10 mg) on EIB could predict the clinical effectiveness of longer term once daily treatment. Methods: This was a prospective, open-label study. Twenty-four asthmatic adolescents (12-17 years) suboptimally controlled by low-dose inhaled corticosteroids, with ≥10% post-exercise fall in FEV1 , were included. They performed an exercise test at baseline, 20 hr after a single MLK-dose and 40-44 hr after the last dose of 4 weeks once daily treatment. The correlations between the effect of a single dose and 4 weeks treatment on area under the curve (AUC) and maximum % fall in FEV1 were calculated. Results: AUC0-20 min decreased significantly after a single MLK-dose (P = 0.001, CI: 64.9-218.2), but not after 4 weeks of treatment (P = 0.080, CI: -12.2 to 200.4). There was a moderate correlation between the effect of a single MLK-dose and 4 weeks treatment on AUC0-20 min , r = 0.49 (P = 0.011), and maximum % fall in FEV1 , r = 0.40 (P = 0.035). Conclusion: The protection provided by a single MLK-dose against EIB only modestly predicts the effect of regular treatment against EIB in adolescent asthmatics on low-dose inhaled corticosteroids. If used on a daily base, MLK offered clinically significant protection against EIB in two thirds of adolescents suboptimally controlled by low-dose ICS. Pediatr Pulmonol. 2015;9999:XX-XX. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Oct 2015 · Pediatric Pulmonology

  • No preview · Article · Oct 2015 · European Respiratory Journal
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    ABSTRACT: Background: Sublingual Immunotherapy (SLIT) is a potential efficacious and safe treatment option for patients with respiratory, IgE-mediated allergic diseases. A combined tolerability, dose finding study with a sublingual liquid birch pollen preparation (SB) was conducted. Methods: 269 adults with birch pollen induced AR were randomized to placebo, SB 3,333; 10,000; 20,000 or 40,000 AUN/ml. Differences in symptom scores following a titrated nasal provocation test (TNPT) at baseline and after 5 months of treatment were determined. Safety, tolerability, birch pollen specific immunoglobulin levels and Peak Nasal Inspiratory Flow (PNIF) were also measured (all measures determined outside the birch pollen season). Results: In all treatment groups an improvement in symptom scores after treatment compared to baseline was observed, with an additional stepwise improvement in the active groups compared to placebo, which was significant in high dose-groups (p=0.008 and p<0.001, respectively). For this primary endpoint, a significant linear dose response curve was observed, the higher the dose the better the improvement observed. Likewise, active treatment resulted in an increase in PNIF and serum IgG levels compared to placebo. The highest improvements were found in the 40,000 AUN/ml group. All active dosages resulted in more adverse reactions than placebo, that were mainly mild and well-controlled. Conclusions: A multi-centre trial evaluated the dose response and tolerability of SB. All active treatment groups showed better responses than placebo for both primary and secondary parameters. The results indicate that, within the studied dose range, SB 40,000 AUN/ml is the most optimal effective and safe dose (ClinicalTrials. gov: NCT01639768). This article is protected by copyright. All rights reserved.
    No preview · Article · Sep 2015 · Allergy

  • No preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: Fractional exhaled nitric oxide (FeNO) is a convenient, non-invasive method for the assessment of active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid diagnosis and monitoring in several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory, infectious, and/or immunological conditions. In this short review, we provide an overview of several clinical studies and discuss the status of potential applications of NO measurements in clinical conditions beyond asthma.
    Full-text · Article · Aug 2015
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    ABSTRACT: Background: Allergen-induced late airway response offers important pharmacodynamic targets, including T helper 2 (TH2) biomarkers. However, detection of inflammatory markers has been limited in dithiothreitol-processed sputum. Objectives: To test whether allergen-induced TH2 inflammatory markers can be reproducibly quantified by sensitive detection techniques in ultracentrifuged sputum and the effect of fluticasone (FP) on these endpoints. Methods: Thirteen allergic asthmatics with dual allergen-induced airway responses, documented during a single-blind placebo run-in period, participated in a double-blind, two-period crossover study. Each period consisted of three consecutive days, separated by ≥3 weeks. Following randomization, subjects inhaled FP (500 µg bid, five doses total) or placebo. On Day 2 in each study period, allergen challenge was performed and airway response measured by forced expiratory volume in 1 sec (FEV1) until 7 h post-challenge. Sputum was induced 24 h pre-allergen and 7 and 24 h post-allergen. Sputum samples were split into two portions: TH2 biomarkers were quantified by Meso Scale multiplex platform following ultracentrifugation, and cell differentials were counted on Giemsa-May-Grünwald-stained cytospins. Allergen-induced changes in inflammatory endpoints were compared between FP and placebo using a mixed model ANCOVA. Results: Inhaled allergen induced dual airway responses in all subjects during both placebo periods with reproducible late asthmatic response (LAR) and increased sputum inflammatory biomarkers (IL-2, IL-4, IL-13, and eotaxin-1) and eosinophil counts. FP effectively blunted both the LAR and the inflammatory biomarkers. Conclusions: Combining novel, sensitive quantification methods with ultracentrifugation allows reproducible quantification of sputum biomarkers following allergen challenge, reversed by FP. This approach allows non-invasive identification of pharmacodynamic targets for anti-asthma therapies.
    Preview · Article · May 2015
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    ABSTRACT: Soluble inflammatory markers obtained from non-invasive airway sampling such as induced sputum may be useful biomarkers for targeted pharmaceutical interventions. However, before these soluble markers can be used as potential targets, their variability and reproducibility need to be established in distinct study populations. This study aimed to assess the reproducibility of biomarkers obtained from induced sputum and serum in chronic smokers and non-smokers. Sputum and serum samples were obtained from 16 healthy non-smokers and 16 asymptomatic chronic smokers (for both groups: 8M/8F, 30-52 years, FEV1 ≥80% pred.; ≥10 pack years for the smokers) on 2 separate visits 4-10 days apart. Soluble markers in serum and sputum were analyzed by ELISA. The differences between smokers vs non-smokers were analyzed with a t-test and variability was assessed on log-transformed data by a mixed model ANOVA. Analyzable sputum samples could be obtained from all 32 subjects. In both study populations neutrophils and macrophages were the predominant cell types. Serum Pulmonary Surfactant Associated Protein D had favorable reproducibility criteria for reliability ratio (0.99), intra-subject coefficient of variation (11.2%) and the Bland Altman limits of agreement. Furthermore, chronic smokers, compared to non-smokers, had significantly higher sputum concentrations of IL-8 (1094.6 pg/mL vs 460.8 pg/mL, p=0.006)), and higher serum concentrations of Pulmonary Surfactant Associated Protein D (110.9 pg/mL vs 64.7 pg/mL, p=0.019), and lower concentrations of Serum Amyloid A (1352.4 pg/mL vs 2297.5 pg/mL, p= 0.022). Serum Pulmonary Surfactant Associated Protein D proved to be a biomarker that fulfilled the criteria for reproducibility in both study groups. Copyright © 2015. Published by Elsevier Ltd.
    No preview · Article · May 2015 · Pulmonary Pharmacology & Therapeutics
  • Amit D Parulekar · Zuzana Diamant · Nicola A Hanania
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    ABSTRACT: Despite guideline-based treatment, many patients with severe asthma continue to have uncontrolled disease. Fungal allergy is being increasingly recognized in the pathogenesis of severe asthma. Limited data exist on the approach to treatment of fungal asthma. This review summarizes existing evidence on the use of antifungal agents in allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS), and highlights needed areas of future investigation. Recent studies evaluating oral triazole therapy in ABPA appear to support triazole use in a carefully considered clinical setting, whereas studies assessing triazole use in SAFS have yielded mixed results. Despite early encouraging findings that oral triazole use may improve asthma symptoms, stabilize lung function, decrease inhaled and systemic corticosteroid requirements, and alter serum biomarkers, overall data are limited. Appropriate patient selection, as well as choice of the optimal drug, dose, frequency, and duration of therapy, remains poorly defined. The role of antifungal therapy in severe asthma remains unclear. Early studies have suggested a possible benefit of some antifungal agents, such as oral triazoles in ABPA and SAFS; however, routine clinical use of these agents in severe asthma without ABPA is not currently recommended. Further research is needed to better delineate the potential utility of antifungal medications in severe asthma and identify the asthma populations who benefit from such treatment.
    No preview · Article · Jan 2015 · Current opinion in pulmonary medicine
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    Herman Pieterse · Zuzana Diamant
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    ABSTRACT: Good clinical practice (GCP) guidelines should always be implemented and obeyed in clinical interventional studies. In this mini-review, we will address several burning questions relating to GCP in a concise ‘frequently asked questions’ format. While compliance to current rules and regulations is our mission, we also wish to play devil's advocate attempting to translate the rules into sizeable chunks using a high dose of common sense.
    Preview · Article · Dec 2014
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    Pradeesh Sivapalan · Zuzana Diamant · Ulrik CS
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    ABSTRACT: PURPOSE OF REVIEW: Obesity has significant impact on asthma incidence and manifestations. The purpose of the review is to discuss recent observations regarding the association between obesity and asthma focusing on underlying mechanisms, clinical presentation, response to therapy and effect of weight reduction. RECENT FINDINGS: Clinical and epidemiological studies indicate that obese patients with asthma may represent a unique phenotype, which is more difficult to control, less responsive to asthma medications and by that may have higher healthcare utilization. A number of common comorbidities have been linked to both obesity and asthma, and may, therefore, contribute to the obese-asthma phenotype. Furthermore, recently published studies indicate that even a modest weight reduction can improve clinical manifestations and outcome of asthma. SUMMARY: Compared with normal-weight patients, obese and overweight patients with asthma have poorer asthma control and respond less to corticosteroid therapy. Future studies focusing on the mechanism underlying both obesity and asthma including the obese-asthma phenotype are required to better characterize the link between the conditions and target the management of this patient group.
    Full-text · Article · Nov 2014 · Current Opinion in Pulmonary Medicine
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    Leif Bjermer · Vibeke Backer · Ronald Dahl · Zuzana Diamant

    Preview · Article · Jun 2014
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    ABSTRACT: Current guidelines recommend chronic obstructive pulmonary disease (COPD) management based on symptoms or health status assessment and lung function parameters. However, COPD is a complex and heterogeneous disease that needs an individualized approach for proper disease management. A structured consultation including health status assessment tools, such as the Clinical COPD Questionnaire and the COPD Assessment Test should improve the quality of the consultation, providing more information than symptoms alone. Both questionnaires are designed to provide the clinician information enabling a more personalized disease approach and subsequent management. Although both Clinical COPD Questionnaire and COPD Assessment Test have good discriminate properties, their use as prognostic markers of severity and their ability to modify disease management has not yet been fully established. New studies are needed to further determine their value on several disease outcomes.
    No preview · Article · Jun 2014 · Expert Review of Respiratory Medicine
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    ABSTRACT: CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses. To investigate the tolerability and pharmacokinetics of setipiprant (ACT-129968), a selective orally active CRTH2 antagonist, in allergic asthmatics and to assess the protective effects of multiple doses of this drug against allergen-induced airway responses. In this 3-centre, double-blinded, placebo-controlled, cross-over study, 18 allergic asthmatic males were randomized to setipiprant 1000 mg or matching placebo b.i.d. for 5 consecutive days. Study periods were separated by a washout of ≥ 3 weeks. On study day 4, subjects underwent a standardized allergen challenge and airway response was recorded by FEV1 until 10 h post-allergen. Airway responsiveness to methacholine and exhaled nitric oxide (eNO) were measured pre- and post-dosing. The effects of both treatments on the allergen-induced airway responses were compared by a paired Student's t-test. Fifteen subjects completed the study per-protocol and were included in the analysis. Overall, setipiprant was well tolerated and no clinically relevant adverse events occurred. Trough plasma concentrations showed a high inter-subject variability. Compared with placebo, setipiprant significantly reduced the allergen-induced late asthmatic response (LAR), inhibiting the area under the response vs. time curve (AUC(3–10 h)) by on average 25.6% (P = 0.006) and significantly protected against the allergen-induced airway hyperresponsiveness (AHR) to methacholine (P = 0.0029). There was no difference in the early asthmatic response (EAR) or in allergen-induced changes in eNO between treatments. Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders.
    No preview · Article · Jun 2014 · Clinical & Experimental Allergy
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    ABSTRACT: Although not yet widely implemented, fraction of exhaled nitric oxide (FeNO) has emerged in recent years as a potentially useful biomarker for the assessment of airway inflammation both in undiagnosed patients with non-specific respiratory symptoms and in those with established airway disease. Research to date essentially suggests that FeNO measurement facilitates the identification of patients exhibiting T-helper cell type 2 (Th2)-mediated airway inflammation, and effectively those in whom anti-inflammatory therapy, particularly inhaled corticosteroids (ICS), is beneficial. In some studies, FeNO-guided management of patients with established airway disease is associated with lower exacerbation rates, improvements in adherence to anti-inflammatory therapy, and the ability to predict risk of future exacerbations or decline in lung function. Despite these data, concerns regarding the applicability and utility of FeNO in clinical practice still remain. This article reviews the current evidence, both supportive and critical of FeNO measurement, in the diagnosis and management of asthma and other inflammatory airway diseases. It additionally provides suggestions regarding the practical application of FeNO measurement: how it could be integrated into routine clinical practice, how its utility could be assessed and its true value to both clinicians and patients could be established. Although some unanswered questions remain, current evidence suggests that FeNO is potentially a valuable tool for improving the personalised management of inflammatory airway diseases.
    Full-text · Article · Jun 2014 · Respiratory medicine
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    ABSTRACT: Chemoattractant receptor-homologous molecule expressed on T helper (Th) 2 cells (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 (PGD2), a key mediator in inflammatory disorders such as asthma and allergic rhinitis. In this study we investigated the single- and multiple-dose tolerability and pharmacokinetics of setipiprant, an orally active, potent, and selective CRTH2 antagonist.This randomized, double-blind, placebo-controled study was performed in two parts in healthy male subjects. In study Part A, single oral doses of up to 2000 mg setipiprant or placebo were given to sequential groups of 8 subjects each. Additionally, the impact of food on the pharmacokinetics was investigated in one dose group. In study Part B, two groups of subjects received 500 or 1000 mg setipiprant or placebo b.i.d. during 5.5 days. At regular intervals, tolerability variables, plasma and urine levels of setipiprant were determined.Setipiprant was well tolerated after single- and multiple-dose administration. Headache was the most frequently reported adverse event. No treatment effect on tolerability variables was observed. After single- and multiple-dose administration setipiprant was rapidly absorbed, and followed a biphasic elimination pattern with an elimination half-life between 10 and 18 h. Steady-state conditions were reached after 2-3 days and setipiprant did not accumulate. Exposure to setipiprant was lower in the presence of food. Urinary excretion of unchanged setipiprant did not exceed 7% of the administered dose.In this entry-into humans study, setipiprant showed good tolerability and a favorable pharmacokinetic profile, thus warranting its development in the treatment of inflammatory disorders.This article is protected by copyright. All rights reserved.
    No preview · Article · Apr 2014 · Fundamental and Clinical Pharmacology
  • F Kanniess · Z Diamant · M Lomax · M Jain

    No preview · Article · Feb 2014 · Pneumologie
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    F. Kanniess · Z. Diamant · M. Lomax · M. Jain
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    ABSTRACT: Background The ICS fluticasone propionate (FP) and the LABA formoterol fumarate (FORM) have now been combined in a single aerosol inhaler (FP/FORM; flutiform®). The effect of low- (2 puffs 50/5 µg bid) vs high-dose (2 puffs 250/10 µg bid) FP/FORM on airway responsiveness to AMP was compared in an incomplete block, placebo-controlled, 2-way crossover study. Post hoc data analysis from patients who received both FP/FORM doses is presented. Methods 62 patients (33M, 29F; =18yrs; reversible FEV1 =60% pred.) discontinued maintenance ICS medication for 2 - 3wks; those showing a provocative dose of AMP producing a 20% decline in FEV1 (AMP PD20 FEV1) of <60 mg were randomised to receive 2 of 3 treatments (FP/FORM high-, low-dose or placebo) during 2 periods of 28 ± 3 days each, separated by 2 - 3wks. AMP challenges were performed pre-dose and repeated 12h after last dose at the end of each treatment period. The difference in changes in AMP PD20 FEV1 (day 1 vs day 28) between treatments were compared by an ANCOVA. Results 15 patients were randomised to receive both high- and low-dose FP/FORM. The change in AMP PD20 FEV1 was greater with FP/FORM high- compared with low-dose (LS means: high dose = 11 mg; 95% CI 4.3, 27.9; low dose = 4.6 mg, 95% CI 1.8, 11.8), with a statistically significant 2.4 fold difference in AMP PD20 FEV1 (1.2 doubling doses) between doses (LS mean: 2.4; 95% CI 1.3, 4.5; p = 0.012). FP/FORM was well-tolerated; only few (mild or moderate) AEs occurred. Conclusions A significant dose-response was found between low- and high-dose FP/FORM with the higher dose demonstrating a greater reduction in airway responsiveness to AMP.
    Preview · Article · Nov 2013 · Thorax

Publication Stats

2k Citations
340.30 Total Impact Points

Institutions

  • 2015
    • Baylor College of Medicine
      Houston, Texas, United States
  • 2013-2015
    • Skåne University Hospital
      Malmö, Skåne, Sweden
    • Lund University
      Lund, Skåne, Sweden
  • 2011-2015
    • University of Groningen
      • Department of General Practice
      Groningen, Groningen, Netherlands
  • 2004-2014
    • Centre for Human Drug Research
      Leyden, South Holland, Netherlands
  • 1997-2012
    • Leiden University Medical Centre
      • Department of Pulmonology
      Leyden, South Holland, Netherlands
  • 2009-2011
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 1999-2010
    • Erasmus Universiteit Rotterdam
      • Department of Pulmonology
      Rotterdam, South Holland, Netherlands
  • 2000
    • Imperial College London
      Londinium, England, United Kingdom
  • 1996-1999
    • Leiden University
      Leyden, South Holland, Netherlands