Publications by authors named "Ricardo Tan"

24 Publications

  • Page 1 of 1

LDL subclass lipidomics in atherogenic dyslipidemia: effect of statin therapy on bioactive lipids and dense LDL.

J Lipid Res 2020 06 15;61(6):911-932. Epub 2020 Apr 15.

Metabolomics Laboratory Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese hypertriglyceridemic hypercholesterolemic males [n = 12; lipoprotein (a) <10 mg/dl] received pitavastatin calcium (4 mg/day) for 180 days in a single-phase unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids {LPC, lysophosphatidylinositol (LPI), lysoalkylphosphatidylcholine [LPC(O)]; 9, 0.2, and 0.14 mol per mole of apoB, respectively; all < 0.001 vs. LDL1-4}, suggesting elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI, and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5-3 mol per mole of apoB; 3-7 mmol per mole of PC) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy.
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http://dx.doi.org/10.1194/jlr.P119000543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269759PMC
June 2020

Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome.

Arterioscler Thromb Vasc Biol 2018 02 28;38(2):438-447. Epub 2017 Dec 28.

From the Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (A.A.K., P.A.M., N.E.S., P.J.N., G.W., R.T., K.H., T.W.N., N.A.M., J.M.W., C.K.B., Z.H.A., G.W.L., B.A.K., P.J.M.); Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia (A.A.K., B.A.K., P.J.M.); Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia (A.A.K.); King Fahad Medical City, Riyadh, Saudi Arabia (Z.H.A.); and School of Biomedical Sciences, University of Western Australia, Perth (T.W.N.).

Objective: High-density lipoprotein (HDL) lipid composition and function may better reflect cardiovascular risk than HDL cholesterol concentration. This study characterized the relationships between HDL composition, metabolism, and function in metabolic syndrome (MetS) patients and how changes in composition after weight loss (WL) and exercise treatments are related to function.

Approach And Results: Plasma samples from MetS patients (n=95) and healthy individuals (n=40) were used in this study. Subsets of the MetS group underwent 12 weeks of no treatment (n=17), WL (n=19), or WL plus exercise (WLEX; n=17). HDL was isolated using density-gradient ultracentrifugation. The HDL lipidome was analyzed by mass spectrometry, and particle size determined by nuclear magnetic resonance. Cholesteryl ester transfer protein activity and ex vivo HDL cholesterol efflux capacity (CEC) were assessed. The HDL lipidome in the MetS patients was substantially different from that in healthy individuals, mean particle size was smaller, and CEC was lower. Several HDL phospholipid and sphingolipid species were associated with HDL diameter and CEC. The HDL lipidome and particle size were modified toward the healthy individuals after WL and WLEX treatments, with greater effects observed in the latter group. Cholesteryl ester transfer protein activity was reduced after WL and WLEX, and CEC was improved after WLEX.

Conclusions: WLEX treatment in MetS patients normalizes the HDL lipidome and particle size profile and enhances CEC. HDL lipids associated with diminished CEC may represent novel biomarkers for early prediction of HDL dysfunction and disease risk and may represent potential therapeutic targets for future HDL therapies.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00163943.
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http://dx.doi.org/10.1161/ATVBAHA.117.310212DOI Listing
February 2018

Corrigendum to "Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice" [Atherosclerosis 243/2 (2015) 598-608].

Atherosclerosis 2016 11;254:314-315

Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2016.01.046DOI Listing
November 2016

Statin action enriches HDL3 in polyunsaturated phospholipids and plasmalogens and reduces LDL-derived phospholipid hydroperoxides in atherogenic mixed dyslipidemia.

J Lipid Res 2016 11 31;57(11):2073-2087. Epub 2016 Aug 31.

Clinical Biochemistry Service, APHP, HUPS, Bicêtre University Hospital, Le Kremlin Bicêtre, France

Atherogenic mixed dyslipidemia associates with oxidative stress and defective HDL antioxidative function in metabolic syndrome (MetS). The impact of statin treatment on the capacity of HDL to inactivate LDL-derived, redox-active phospholipid hydroperoxides (PCOOHs) in MetS is indeterminate. Insulin-resistant, hypertriglyceridemic, hypertensive, obese males were treated with pitavastatin (4 mg/day) for 180 days, resulting in marked reduction in plasma TGs (-41%) and LDL-cholesterol (-38%), with minor effects on HDL-cholesterol and apoAI. Native plasma LDL (baseline vs. 180 days) was oxidized by aqueous free radicals under mild conditions in vitro either alone or in the presence of the corresponding pre- or poststatin HDL2 or HDL3 at authentic plasma mass ratios. Lipidomic analyses revealed that statin treatment i) reduced the content of oxidizable polyunsaturated phosphatidylcholine (PUPC) species containing DHA and linoleic acid in LDL; ii) preferentially increased the content of PUPC species containing arachidonic acid (AA) in small, dense HDL3; iii) induced significant elevation in the content of phosphatidylcholine and phosphatidylethanolamine (PE) plasmalogens containing AA and DHA in HDL3; and iv) induced formation of HDL3 particles with increased capacity to inactivate PCOOH with formation of redox-inactive phospholipid hydroxide. Statin action attenuated LDL oxidability Concomitantly, the capacity of HDL3 to inactivate redox-active PCOOH was enhanced relative to HDL2, consistent with preferential enrichment of PE plasmalogens and PUPC in HDL3.
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http://dx.doi.org/10.1194/jlr.P068585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087874PMC
November 2016

Plasmalogen modulation attenuates atherosclerosis in ApoE- and ApoE/GPx1-deficient mice.

Atherosclerosis 2015 Dec 26;243(2):598-608. Epub 2015 Oct 26.

Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia; Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Australia. Electronic address:

Background And Aim: We previously reported a negative association of circulating plasmalogens (phospholipids with proposed atheroprotective properties) with coronary artery disease. Plasmalogen modulation was previously demonstrated in animals but its effect on atherosclerosis was unknown. We assessed the effect of plasmalogen enrichment on atherosclerosis of murine models with differing levels of oxidative stress.

Methods And Results: Six-week old ApoE- and ApoE/glutathione peroxidase-1 (GPx1)-deficient mice were fed a high-fat diet with/without 2% batyl alcohol (precursor to plasmalogen synthesis) for 12 weeks. Mass spectrometry analysis of lipids showed that batyl alcohol supplementation to ApoE- and ApoE/GPx1-deficient mice increased the total plasmalogen levels in both plasma and heart. Oxidation of plasmalogen in the treated mice was evident from increased level of plasmalogen oxidative by-product, sn-2 lysophospholipids. Atherosclerotic plaque in the aorta was reduced by 70% (P = 5.69E-07) and 69% (P = 2.00E-04) in treated ApoE- and ApoE/GPx1-deficient mice, respectively. A 40% reduction in plaque (P = 7.74E-03) was also seen in the aortic sinus of only the treated ApoE/GPx1-deficient mice. Only the treated ApoE/GPx1-deficient mice showed a decrease in VCAM-1 staining (-28%, P = 2.43E-02) in the aortic sinus and nitrotyrosine staining (-78%, P = 5.11E-06) in the aorta.

Conclusion: Plasmalogen enrichment via batyl alcohol supplementation attenuated atherosclerosis in ApoE- and ApoE/GPx1-deficient mice, with a greater effect in the latter group. Plasmalogen enrichment may represent a viable therapeutic strategy to prevent atherosclerosis and reduce cardiovascular disease risk, particularly under conditions of elevated oxidative stress and inflammation.
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http://dx.doi.org/10.1016/j.atherosclerosis.2015.10.096DOI Listing
December 2015

Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia.

J Lipid Res 2015 Dec 20;56(12):2381-92. Epub 2015 Oct 20.

Dyslipidemia and Atherosclerosis Research Unit, INSERM UMR-S939, and University of Pierre and Marie Curie, Pitie-Salpetriere University Hospital, Paris, France.

The impact of statin treatment on the abnormal plasma lipidome of mixed dyslipidemic patients with metabolic syndrome (MetS), a group at increased risk of developing diabetes, was evaluated. Insulin-resistant hypertriglyceridemic hypertensive obese males (n = 12) displaying MetS were treated with pitavastatin (4 mg/day) for 180 days; healthy normolipidemic age-matched nonobese males (n = 12) acted as controls. Statin treatment substantially normalized triglyceride (-41%), remnant cholesterol (-55%), and LDL-cholesterol (-39%), with minor effect on HDL-cholesterol (+4%). Lipidomic analysis, normalized to nonHDL-cholesterol in order to probe statin-induced differences in molecular composition independently of reduction in plasma cholesterol, revealed increment in 132 of 138 lipid species that were subnormal at baseline and significantly shifted toward the control group on statin treatment. Increment in alkyl- and alkenylphospholipids (plasmalogens) was prominent, and consistent with significant statin-induced increase in plasma polyunsaturated fatty acid levels. Comparison of the statin-mediated lipidomic changes in MetS with the abnormal plasma lipidomic profile characteristic of prediabetes and T2D in the Australian Diabetes, Obesity, and Lifestyle Study and San Antonio Family Heart Study cohorts by hypergeometric analysis revealed a significant shift toward the lipid profile of controls, indicative of a marked trend toward a normolipidemic phenotype. Pitavastatin attenuated the abnormal plasma lipidome of MetS patients typical of prediabetes and T2D.
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http://dx.doi.org/10.1194/jlr.P061143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655992PMC
December 2015

Clinical utility and development of the fluticasone/formoterol combination formulation (Flutiform(®)) for the treatment of asthma.

Drug Des Devel Ther 2014 30;8:1555-61. Epub 2014 Sep 30.

David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Pharmacologic treatment of asthma should be done with a stepwise approach recommended in treatment guidelines. If inhaled corticosteroids (ICSs) alone are not adequate, ICSs in combination with long-acting β-agonists (LABAs) are now established and widely used as the next step in effective controller therapy. Fixed-dose ICS/LABA combinations in a single device are the preferred form of delivery and improve compliance by enabling patients to get symptom relief from the LABA while receiving the anti-inflammatory benefits of ICSs. Fluticasone propionate/formoterol fumarate is one of the newest fixed-dose combinations. It has been in use in Europe in 2012, but is still under regulatory review in the US. Fluticasone is a synthetic ICS with potent anti-inflammatory effects, while formoterol is a selective β2-adrenergic receptor agonist with a rapid onset of bronchodilation within 5-10 minutes and a 12-hour duration of action. Fluticasone/formoterol has shown superior efficacy when compared to fluticasone or formoterol alone in multiple well-designed studies. The combination has shown comparable or "noninferior" benefits in lung function, clinical symptoms, and asthma control when compared with fluticasone and formoterol administered concurrently in separate inhalers. Fluticasone/formoterol provides similar efficacy with fluticasone/salmeterol, but with more rapid symptom relief. It has been compared directly with budesonide/formoterol with comparable results. Fluticasone/formoterol is well tolerated, with no unusual or increased safety concerns versus each individual component or other available ICS/LABA combinations. Fluticasone/formoterol is the latest entry into a relatively crowded market of branded fixed-dose preparations. Upcoming generic fixed-dose combinations and once-daily agents pose significant market challenges. In clinical practice, most practitioners consider all the currently available fixed-dose preparations to be of comparable efficacy and safety.
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http://dx.doi.org/10.2147/DDDT.S36556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196884PMC
July 2015

Is a single blood eosinophil count a reliable marker for "eosinophilic asthma?".

J Asthma 2012 Oct 20;49(8):807-10. Epub 2012 Aug 20.

Department of Medicine, UCLA Medical Center, Los Angeles, CA 90095, USA.

Introduction: "Eosinophilic asthma" refers to an asthma phenotype characterized by predominance of eosinophils in the bronchial airways and corticosteroid responsiveness. Recent clinical trials of eosinophil-blocking agents have utilized a blood eosinophil count of 300 or 400 eosinophils/mm(3) or higher to identify subjects with moderate to severe asthma. We observed multiple instances of counts which varied widely in the same patient within the same day.

Objectives: To determine whether there is significant variability in blood eosinophil counts taken throughout the day in the same patients with moderate asthma.

Methods: Twelve subjects had serial blood eosinophil counts obtained within a 24-hour period.

Results: Twelve subjects were enrolled: seven subjects had moderate asthma, three subjects had mild asthma, and two control subjects had no asthma. The variability of blood eosinophil counts ranged from 17% to 396%. No specific diurnal pattern was found among the subjects. The highest variability were seen in three moderate asthmatics (396%, 170%, and 154%) and one mild asthmatic (164%) while the other subjects had variability of 84% or less.

Conclusions: This study showed significant variability in blood eosinophil counts within a 24-hour period in the same subjects. The highest variability was seen in moderate asthmatics. These findings would appear to place the utility of a single eosinophil count in question.
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http://dx.doi.org/10.3109/02770903.2012.713428DOI Listing
October 2012

Exercise-induced bronchoconstriction update: therapeutic management.

Allergy Asthma Proc 2012 Jan-Feb;33(1):7-12

University of California, Los Angeles, Medical Center, Los Angeles, California 90025, USA.

Management of exercise-induced bronchoconstriction (EIB) should include both prevention and treatment directed toward the underlying asthma and bronchial hyperresponsiveness. Both nonpharmacologic and pharmacologic approaches should be followed. Preexercise warm-up, to take advantage of the refractory period that follows EIB, is an important preventive technique. Dietary interventions such as fish oil, vitamin D, and ascorbic acid have shown promising results. Beta 2-agonists are considered the most effective agents for EIB at this time but intermittent use is recommended to avoid tolerance or decreased effectiveness with daily regular use. Leukotriene inhibitors and mast cell stabilizing agents can be useful in EIB but are less effective than beta 2-agonists. Tolerance to beta 2-agonists is not prevented by concomitant use of inhaled corticosteroid but it is not known whether use of leukotriene inhibitors can affect tolerance. EIB in elite athletes with no underlying asthma may have a different pathogenesis.
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http://dx.doi.org/10.2500/aap.2012.33.3497DOI Listing
July 2012

Omalizumab in the treatment of asthma.

Expert Rev Respir Med 2011 Dec;5(6):747-56

California Allergy and Asthma Medical Group Inc., 11645 Wilshire Boulevard, Suite 1155, Los Angeles, CA 90025, USA.

Omalizumab was introduced in 2003 and is the first asthma drug to target IgE, the allergic antibody that initiates the allergic cascade. Well-controlled studies and post-marketing clinical experience have shown it to be an effective and safe medication. Treatment guidelines now recommend omalizumab as an add-on option for patients with moderate-to-severe allergic asthma uncontrolled on high-dose inhaled corticosteroids and long-acting β-agonists. Despite initial concerns, there is no evidence of any association with malignancy at this time. In our opinion, omalizumab is well-tolerated and significantly improves pulmonary function, decreases clinical symptoms and improves the quality of life in patients with uncontrolled allergic asthma.
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http://dx.doi.org/10.1586/ers.11.73DOI Listing
December 2011

The relationship of rhinitis and asthma, sinusitis, food allergy, and eczema.

Immunol Allergy Clin North Am 2011 Aug;31(3):481-91

California Allergy and Asthma Medical Group, 11645 Wilshire Boulevard, Suite 1155, Los Angeles, CA 90025, USA.

Epidemiologic, genetic, immunologic, and clinical studies show a close relationship between allergic rhinitis and asthma, food allergy, and atopic dermatitis. Rhinitis and sinusitis often coexist and are commonly referred to with the term rhinosinusitis. These conditions are also linked in the so-called atopic march, which is the sequential appearance of atopic manifestations starting with atopic dermatitis and later followed by food allergy, allergic rhinitis, and asthma. Allergic rhinitis and asthma are now increasingly being approached diagnostically and therapeutically as the one-airway concept.
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http://dx.doi.org/10.1016/j.iac.2011.05.010DOI Listing
August 2011

Safety of omalizumab in asthma.

Expert Opin Drug Saf 2011 May 15;10(3):463-71. Epub 2011 Mar 15.

California Allergy and Asthma Medical Group, 11645 Wilshire Blvd., Suite 1155, Los Angeles, CA 90025, USA.

Introduction: Omalizumab is the first mAb to be introduced for the management of asthma. It is also the first agent designed to block the effects of IgE in initiating the allergic cascade resulting in asthma manifestations. Introduced in 2003, it is now widely used as an effective therapeutic tool in moderate-to-severe allergic asthmatics who are uncontrolled on maximal conventional therapy, including high-dose inhaled steroids and long-acting β-agonists. There is still understandable concern regarding the long-term effects of this drug.

Areas Covered: The authors provide a review of safety data generated by controlled clinical trials and post-marketing surveillance as well as a brief overview of the clinical indications and efficacy of omalizumab. They also address specific issues of concern, including the risk of anaphylaxis and malignancy. The reader will gain a working knowledge of the role of omalizumab in current guidelines for the management of asthma.

Expert Opinion: Omalizumab appears to be safe and well-tolerated. The possible association of malignancy with omalizumab has been of the greatest concern to patients and physicians. Analysis of clinical study data shows that this incidence is rare and the relative risk of cancer with omalizumab is not significantly different from that which is expected in the general population of people with asthma. As part of a relatively new class of agents, continued surveillance is needed as its indications expand and its use in the population continues to grow.
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http://dx.doi.org/10.1517/14740338.2011.563840DOI Listing
May 2011

Fatal consequence of allergic rhinitis.

J Allergy Clin Immunol 2010 Nov;126(5):1077

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http://dx.doi.org/10.1016/j.jaci.2010.07.017DOI Listing
November 2010

Comparison of olopatadine 0.6% nasal spray versus fluticasone propionate 50 microg in the treatment of seasonal allergic rhinitis.

Allergy Asthma Proc 2009 May-Jun;30(3):255-62

Institute for Allergy and Asthma, Chevy Chase, Maryland 20817, USA.

The efficacy of nasal antihistamines (NAHs) for allergic rhinitis (AR) is comparable with or better than second-generation oral antihistamines, with faster onset of action and greater effect on congestion. Limited data suggest that NAHs may be equivalent to intranasal corticosteroids at reducing the full range of nasal seasonal AR (SAR) symptoms, including congestion. The efficacy of olopatadine 0.6% nasal spray (2 sprays/nostril b.i.d.) for symptoms of SAR was compared with fluticasone 50 microg nasal spray (2 sprays/nostril q.d.) in a double-blind, randomized, parallel-group, 2-week noninferiority trial. A total of 130 symptomatic patients were randomized to treatment and they recorded nasal and ocular allergy symptom scores b.i.d. (morning and evening) in a diary. Both treatments reduced reflective and instantaneous assessments of nasal and ocular symptoms from baseline throughout the 2-week study period (p < 0.05). The reflective total nasal symptom score (the primary efficacy variable) decreased by an average of -45.4% for patients treated with olopatadine 0.6% and by -47.4% for those treated with fluticasone; statistical significance favoring olopatadine was demonstrated at day 1. No significant between-treatment differences were determined for the average 2-week percent changes from baseline for congestion, runny nose, sneezing, itchy nose, and ocular symptoms, although olopatadine had a faster onset of action for reducing all symptoms. Both treatments were safe and well tolerated. Olopatadine and fluticasone nasal sprays both reduced nasal and ocular SAR symptoms with no significant between-treatment differences except for a faster and greater onset of action with olopatadine.
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http://dx.doi.org/10.2500/aap.2009.30.3232DOI Listing
August 2009

Mometasone furoate in the management of asthma: a review.

Ther Clin Risk Manag 2008 Dec;4(6):1201-8

California Allergy and Asthma Medical Group, Los Angeles, CA;

Inhaled corticosteroids (ICS) have proven to be the most effective and essential therapy for the treatment of bronchial asthma. The 2007 National Asthma Education and Prevention Program guidelines recommend ICS as preferred therapy for patients with mild to severe persistent asthma. Mometasone furoate (MF) is a relatively new ICS agent with high affinity for the glucocorticoid receptor. It is approved in the US for maintenance treatment of asthma for patients 4 years of age and older. It has been shown to be well tolerated with no significant adverse side effects observed in clinical trials and post-marketing surveillance. The efficacy of mometasone furoate has been established in large, well-designed studies. In patients with persistent asthma previously treated either with short-acting beta-agonists alone or twice-daily maintenance therapy with ICS, once-daily MF has been shown to be superior to placebo in improving lung function, symptom control, and quality of life; and has shown comparable efficacy compared with budesonide, beclomethasone, and fluticasone. Twice-daily dosing with MF has been demonstrated to successfully allow for reduction or elimination of oral corticosteroids in severe asthmatics.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643101PMC
http://dx.doi.org/10.2147/tcrm.s3261DOI Listing
December 2008

Omalizumab also successful in chronic urticaria.

J Allergy Clin Immunol 2008 Mar;121(3):784; author reply 784-5

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http://dx.doi.org/10.1016/j.jaci.2007.12.1174DOI Listing
March 2008

Pediatric sinusitis.

Curr Allergy Asthma Rep 2007 Nov;7(6):421-6

California Allergy and Asthma Medical Group, 11645 Wilshire Boulevard, Suite 1155, Los Angeles, CA 90025, USA.

Although sinusitis is one of the most common problems encountered in clinical practice, it can be a challenge to diagnose and treat appropriately. Sinusitis refers to inflammation (infectious or noninfectious) in the paranasal sinuses. Infectious sinusitis can be bacterial or viral. This article focuses on bacterial sinusitis. Acute bacterial sinusitis usually follows a viral upper respiratory infection (URI) but can also present with severe symptoms 3 to 5 days after onset. Chronic sinusitis has less prominent symptoms and can be easily missed. When antibiotic therapy is warranted, the antibiotic should be chosen based on knowledge of antimicrobial resistance in specific geographic areas and populations. Adjunctive measures include saline irrigation, steam inhalation, nasal and systemic steroids, mucolytics, and decongestants. It is important to identify and treat predisposing factors, including viral URIs, allergic rhinitis, nasal structural abnormalities, gastroesophageal reflux disease, and immune deficiencies.
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http://dx.doi.org/10.1007/s11882-007-0064-5DOI Listing
November 2007

Effect of omalizumab on patients with chronic urticaria.

Ann Allergy Asthma Immunol 2007 Aug;99(2):190-3

Division of Clinical Allergy and Immunology, UCLA Medical Center, Los Angeles, California, USA.

Background: Chronic urticaria (CU) is often difficult to treat. Approximately 40% to 50% of patients with no apparent cause are believed to have an associated autoimmune profile that may play a pathogenetic role.

Objectives: To describe 3 patients with CU refractory to conventional treatment who responded to omalizumab therapy.

Methods: Treatment was maximized with antihistamines, antileukotrienes, and histamine2 blockers with no improvement. Systemic steroids provided only temporary relief. Laboratory workup revealed 1 patient with a low IgE level and elevated anti-IgE receptor antibody level, 1 patient with an elevated IgE level but a normal anti-IgE receptor antibody level, and 1 patient with a very elevated IgE level and an elevated anti-IgE receptor antibody level. All 3 patients were prescribed omalizumab therapy every 2 weeks.

Results: Two patients had total clearing of urticaria within 1 week and 1 patient within 6 weeks of starting omalizumab therapy. The patient with the elevated anti-IgE receptor antibody level had normalization of the level after starting treatment.

Conclusions: Omalizumab may have a beneficial effect in the treatment of CU. Further studies are needed to confirm this effect and better elucidate the mechanism for the observed improvement.
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http://dx.doi.org/10.1016/S1081-1206(10)60644-8DOI Listing
August 2007

Effectiveness of montelukast in the treatment of cough variant asthma.

Ann Allergy Asthma Immunol 2004 Sep;93(3):232-6

Division of Clinical Allergy and Immunology, UCLA School of Medicine, Los Angeles, California, USA.

Background: Antileukotriene agents have been shown to be beneficial in chronic asthma. Although patients with cough variant asthma have cough with minimal wheezing and dyspnea, airway hyperresponsiveness from chronic inflammation is believed to be the underlying mechanism.

Objective: To evaluate the effectiveness of montelukast, a leukotriene receptor antagonist, in the treatment of cough variant asthma.

Methods: Fourteen patients with cough variant asthma participated in a randomized, double-blind, placebo-controlled trial with a 7- to 10-day baseline period and a 4-week treatment period with montelukast, 10 mg, or placebo daily. Inclusion criteria were (1) chronic cough with a duration of at least 4 weeks with minimal or no wheezing or dyspnea and (2) forced expiratory volume in 1 second of 50% to 85% of predicted and reversibility of 12% with use of an inhaled beta-agonist or forced expiratory volume in 1 second greater than 85% and positive methacholine challenge results. Patients fulfilled the minimum criteria for cough frequency and symptom scores for randomization.

Results: Eight patients received montelukast and 6 received placebo. The primary efficacy variable, mean percentage change from baseline in cough frequency, was significantly improved by the second week, and by the fourth week the mean percentage change from baseline was 75.7% for the treatment group and 20.7% for the placebo group.

Conclusions: The leukotriene receptor antagonist montelukast seems to be effective in the treatment of cough variant asthma. Larger studies are recommended to confirm this effect.
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http://dx.doi.org/10.1016/S1081-1206(10)61493-7DOI Listing
September 2004

Provocation studies in the diagnosis of occupational asthma.

Immunol Allergy Clin North Am 2003 May;23(2):251-67

California Allergy and Asthma Medical Group, 11645 Wilshire Boulevard, Suite 1090, Los Angeles, CA 90025, USA.

Specific and nonspecific provocation studies, although not always essential for diagnosing OA, help confirm the diagnosis and identify the offending agent. Nonspecific bronchial challenge testing is used to detect airway hyperresponsiveness and to clarify the nature of the patient's symptoms. Pharmacologic bronchoconstrictor agents (eg, methacholine, histamine) most commonly are used for the challenge, but nonisotonic aerosols, exercise and hyperventilation also can show airway hyperresponsiveness. Nonspecific challenges usually are done in the laboratory, but can be done at the workplace if emergency equipment is available. A comparison of results obtained at and away from the workplace (at least 1 week apart) may be helpful in diagnosing OA. Specific bronchial challenge testing is considered the gold standard for OA diagnosis. It can be crucial in helping physicians, employers, and employees make decisions about continued employment, compensation, career changes, and treatment. Testing can pinpoint new industrial agents that cause OA, enabling dissemination of information on its hazards to the public and within the industry. The nature of the agent determines the type of protocol that is used for testing. Agents can be in the form of dusts, powders, aerosols, vapors gases, and animal dander. Exposure can be as simple as having patients simulate their work activities, or as complicated as using special challenge chambers with controlled environments and precise delivery of agents. Performing control challenges with a component that is separate from the test agent is essential to avoid false-positive results. The timing, duration, and dosing of exposure depend on the type of reaction that has been experienced previously, the nature of the agent, and the patient's baseline airway hyperresponsiveness. Serial spirometry and observation often are done for up to 8 hours to monitor early and late reactions. SBC testing should be performed in the proper medical setting in which emergency equipment available and should be administered only by healthcare personnel who are trained and experienced in the procedures. Safety of the patient is the primary consideration.
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http://dx.doi.org/10.1016/s0889-8561(02)00080-2DOI Listing
May 2003

Exercise-induced asthma: diagnosis and management.

Ann Allergy Asthma Immunol 2002 Sep;89(3):226-35; quiz 235-7, 297

California Allergy & Asthma Medical Group, Inc, Los Angeles 90025, USA.

Objective: To review the diagnosis and management of exercise-induced asthma (EIA).

Data Sources: Computer-assisted literature searches on MEDLINE for articles, abstracts, and other relevant data on exercise-induced asthma

Study Selection: Published articles, abstracts, and conference proceedings were selected.

Results: EIA is seen in 40 to 90% of asthmatic patients. Exercise can be the sole trigger or be one of multiple triggers of asthma exacerbations. A good history and physical examination can diagnose most cases of EIA. Spirometry can confirm the diagnosis. Exercise testing may be necessary in certain cases. Prevention through both pharmacologic and nonpharmacologic measures is the key to EIA management. Inhaled beta-agonists remain the medications of choice for EIA prophylaxis. Inhaled cromolyn and antileukotrienes are alternatives. Good long-term control of asthma with anti-inflammatory medications such as inhaled steroids will also decrease the incidence of EIA.

Conclusions: Early diagnosis and proper preventive and maintenance therapy can reduce episodes of EIA and enable patients to continue to engage in sports and lead an active life.
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http://dx.doi.org/10.1016/S1081-1206(10)61948-5DOI Listing
September 2002