Phillip Korenblat - Academia.edu (original) (raw)
Papers by Phillip Korenblat
The Journal of Allergy and Clinical Immunology, Feb 1, 2018
RATIONALE: Reslizumab (RES), a humanized anti-interleukin-5 monoclonal antibody, significantly re... more RATIONALE: Reslizumab (RES), a humanized anti-interleukin-5 monoclonal antibody, significantly reduced the risk of clinical asthma exacerbation (CAE) in patients with inadequately controlled eosinophilic asthma and > _1 CAE in the prior 12 months, with greater treatment effect in patients with more historical CAEs. The objective of this analysis was to assess the association between baseline CAE rate and lung function (FEV 1 change from baseline). METHODS: This was a post-hoc analysis of two duplicate 52-wk, placebo (PBO)-controlled phase 3 trials of RES (3 mg/kg IV Q4W). Differences between PBO and RES groups in change in FEV 1 are reported for subgroups of prior CAE history (1 to > _4 CAE in previous 12 months). RESULTS: Of 953 patients, 559 had 1 historical CAE, 193 had 2 historical CAE, 80 had 3 historical CAE, and 115 had > _4 CAE. Trends towards lower FEV 1 at baseline and greater FEV 1 treatment effect over 52 weeks were observed in RES vs PBO in patients with more historical CAEs: 1 historical CAE (baseline 2046mL, diff over 52 weeks 69mL, p50.0124), 2 historical CAE (baseline 1972mL, diff over 52 weeks 139mL, p50.0140), 3 historical CAE (baseline 1833mL, diff over 52 weeks 138mL, p50.0494), > _4 historical CAE (baseline 1837mL, diff over 52 weeks 205mL, p50.0110). CONCLUSIONS: RES was consistently effective at improving FEV 1 in all historical CAE subgroups. RES treatment effects on CAE rate and FEV 1 appear to be related, suggesting a possible physiologic association between exacerbations and lung function in patients with severe eosinophilic asthma.
Annals of Allergy Asthma & Immunology, Nov 1, 2021
Allergy and Asthma Proceedings, May 1, 2010
The corticosteroid budesonide and the long-acting How do the two drugs work? β2-adrenoceptor agon... more The corticosteroid budesonide and the long-acting How do the two drugs work? β2-adrenoceptor agonist formoterol have been combined Budesonide and formoterol target different aspects of into a single pressurized metered-dose inhaler (pMDI). asthma pathology. [4] Budesonide has potent anti-The combination pMDI improves lung function, asthma inflammatory activity, particularly on epithelial cells in the control, asthma symptoms and asthma-related quality of airways. Formoterol, a potent, selective β2-adrenoceptor life outcomes in patients with persistent asthma that is agonist, provides rapid and long-lasting bronchodilatory mild to moderate or moderate to severe. Adapted from activity. When administered together, the effects of the Drugs 2008; 68 (13): 1865-64. [1] two agents are complementary and additive. [4] Budesonide/formoterol pMDI provides a rapid Step 2 Low-dose inhaled corticosteroid (ICS) Step 1 Inhaled short-acting β 2-adrenoceptor agonist as required for symptom relief (use at each treatment step depending on severity of symptoms) Step 4 Medium-dose ICS plus LABA Step 5 High-dose ICS plus LABA and Consider omalizumab in patients with allergies Step 6 High-dose ICS plus LABA plus oral corticosteroid and Consider omalizumab in patients with allergies Adis Data Information BV 2009 Step 3 Low-dose ICS plus inhaled long-acting β 2-adrenoceptor agonist (LABA) or Medium-dose ICS Stepwise preferred long-term management of asthma in patients aged ≥12 y. Based on US National Heart, Lung and Blood Institutes 2007 guidelines for the diagnosis and management of asthma. [2] Start treatment at the step most appropriate to asthma severity and maintain control by stepping up or down treatment when appropriate.
Journal of Asthma, Jan 20, 2020
Objective: A new epinephrine hydrofluoroalkane (HFA) asthma metered-dose inhaler (MDI) was reform... more Objective: A new epinephrine hydrofluoroalkane (HFA) asthma metered-dose inhaler (MDI) was reformulated to replace the previously marketed epinephrine chlorofluorocarbon (CFC) MDI. In addition to the HFA propellant change, several enhanced modifications (i.e. changed from solution to suspension, 43% dose reduction, etc.) were made to the formulation of epinephrine HFA MDI. This study evaluates the 6-month long-term safety and efficacy profile of the new epinephrine HFA MDI. Method: The long-term safety study consists of two 3-month, multi-center, double-or evaluator-blinded, parallel-group, placebo, and active controlled stages. In each stage, subjects aged !12 years with intermittent or mild-to-moderate persistent asthma were randomized to receive epinephrine HFA (2 Â 125 mcg/inhalation), placebo HFA, or epinephrine CFC (2 Â 220 mcg/inhalation). Bronchodilator efficacy was assessed in Stage 1 and was determined primarily by the change in the forced expiratory volume in 1 s (DFEV1) at Week 12, relative to the same day baseline. Results: The primary efficacy endpoint (AUC 0-6hrs of %DFEV1 at Week 12) for epinephrine HFA (47.3 ± 54.2) closely paralleled those for the active control, epinephrine CFC (41.0 ± 43.4). Both groups were found to be overall comparable in bronchodilator efficacy. Both also showed low incidence rates of AEs with tremor being most commonly reported for epinephrine HFA. All AEs found were non-serious and non-significant. The observed changes in vital signs, ECG, serum glucose, and potassium were minimal and not clinically relevant. Conclusion: This study demonstrated that the new epinephrine HFA is overall comparable, in both safety and efficacy, to the previous epinephrine CFC.
J Allerg Clin Immunol, 1991
American Journal of Managed Care, Sep 1, 1996
JAMA: The Journal of the American Medical Association, 1975
In Reply.— The letter of Drs Rothstein and Shapiro regarding our article, "Status Asthmaticu... more In Reply.— The letter of Drs Rothstein and Shapiro regarding our article, "Status Asthmaticus" (231:1277, 1975), makes several important points on which we wish to comment. First, we would emphasize that our remarks were directed mainly at the adult asthmatic patient. The distinction between the adult and small child is important because, as Drs Rothstein and Shapiro imply, children may be more responsive to sympathomimetic agents. Also, significant metabolic acidosis accompanying status asthmaticus is not uncommon in children, whereas it is unusual in adults. We agree that vigorous hydration and large doses of antiinflammatory corticosteroids may result in fluid retention and that caution is warranted, especially in the patient with underlying cardiac disease. Indeed, attention to daily weights and to fluid intake and output are crucial for the avoidance of overhydration and pulmonary edema. In suggesting a dosage of steroids, we were not recommending hydrocortisone necessarily as the steroid of
The Journal of family practice, 1999
Zafirlukast is an oral leukotriene receptor antagonist used in the treatment of patients with mil... more Zafirlukast is an oral leukotriene receptor antagonist used in the treatment of patients with mild to moderate asthma. To investigate its effects in a clinical practice setting, we evaluated zafirlukast in a heterogeneous group of patients who had asthma of different degrees of severity and who were receiving concomitant asthma medications. A total of 3759 patients were enrolled at 924 sites. Patients received zafirlukast 20 mg twice a day for 4 weeks. Pulmonary function was measured twice a day, and overall asthma symptom scores, number of nighttime awakenings, severity of morning asthma symptoms, and beta2-agonist use were recorded daily. In the efficacy analysis (3207 evaluable patients), all parameters showed statistically significant improvement that continued throughout the 4 weeks of the trial. A total of 71% of patients had improved pulmonary function and 72% had improved asthma symptoms. Improvement was consistent regardless of asthma severity category and regardless of con...
Current Allergy and Asthma Reports, 2007
Antileukotriene drugs have been studied for more than 15 years. In this review we examine the rol... more Antileukotriene drugs have been studied for more than 15 years. In this review we examine the role of leukotrienes in rhinitis and rhinosinusitis, and explore the clinical literature supporting the use of antileukotriene agents in these diseases. Although these medications clearly are effi cacious in rhinitis, it is unclear where in the armamentarium they should be used. The evidence for use in sinusitis has not been well studied except in sinusitis-associated aspirinexacerbated respiratory disease. In this circumstance there is information that allows use of antileukotriene agents to be considered effi cacious. We provide our rationale for use and await future clinical studies to answer this important question.
Journal of Allergy and Clinical Immunology, 1996
Journal of Allergy and Clinical Immunology, 1987
Adverse reactions to the tricyclic antidepressant drugs imipramine and desipramine have been desc... more Adverse reactions to the tricyclic antidepressant drugs imipramine and desipramine have been described and include eosinophilia, pulmonary infiltrates with eosinophilia, and elevated total serum IgE levels. The immunologic mechanism accounting for these adverse reactions has not been elucidated. This article describes a patient manifesting bronchospasm, profound eosinophilia, and elevated serum IgE levels after therapy with desipramine that resolved rapidly after withdrawal of the drug. Immunologic investigations failed to demonstrate specific IgE directed against a protein conjugate of desipramine but demonstrated the ability of desipramine to induce mast cell degranulation with direct intradermal skin challenges.
Journal of Allergy and Clinical Immunology, 2003
ceptibility haplotypes than those more exceptional patients with limited numbers of B cells who h... more ceptibility haplotypes than those more exceptional patients with limited numbers of B cells who have not, which suggests that the disease may be different between these two groups.
JAMA: The Journal of the American Medical Association, 1975
Archives of Internal Medicine, 1984
Osteoporosis International, 1993
Journal of Allergy and Clinical Immunology, 2022
Journal of Allergy and Clinical Immunology, 2016
C33. CLINICAL PROFILES AND SEVERITY OF ASTHMA, 2011
The Journal of Allergy and Clinical Immunology, Feb 1, 2018
RATIONALE: Reslizumab (RES), a humanized anti-interleukin-5 monoclonal antibody, significantly re... more RATIONALE: Reslizumab (RES), a humanized anti-interleukin-5 monoclonal antibody, significantly reduced the risk of clinical asthma exacerbation (CAE) in patients with inadequately controlled eosinophilic asthma and > _1 CAE in the prior 12 months, with greater treatment effect in patients with more historical CAEs. The objective of this analysis was to assess the association between baseline CAE rate and lung function (FEV 1 change from baseline). METHODS: This was a post-hoc analysis of two duplicate 52-wk, placebo (PBO)-controlled phase 3 trials of RES (3 mg/kg IV Q4W). Differences between PBO and RES groups in change in FEV 1 are reported for subgroups of prior CAE history (1 to > _4 CAE in previous 12 months). RESULTS: Of 953 patients, 559 had 1 historical CAE, 193 had 2 historical CAE, 80 had 3 historical CAE, and 115 had > _4 CAE. Trends towards lower FEV 1 at baseline and greater FEV 1 treatment effect over 52 weeks were observed in RES vs PBO in patients with more historical CAEs: 1 historical CAE (baseline 2046mL, diff over 52 weeks 69mL, p50.0124), 2 historical CAE (baseline 1972mL, diff over 52 weeks 139mL, p50.0140), 3 historical CAE (baseline 1833mL, diff over 52 weeks 138mL, p50.0494), > _4 historical CAE (baseline 1837mL, diff over 52 weeks 205mL, p50.0110). CONCLUSIONS: RES was consistently effective at improving FEV 1 in all historical CAE subgroups. RES treatment effects on CAE rate and FEV 1 appear to be related, suggesting a possible physiologic association between exacerbations and lung function in patients with severe eosinophilic asthma.
Annals of Allergy Asthma & Immunology, Nov 1, 2021
Allergy and Asthma Proceedings, May 1, 2010
The corticosteroid budesonide and the long-acting How do the two drugs work? β2-adrenoceptor agon... more The corticosteroid budesonide and the long-acting How do the two drugs work? β2-adrenoceptor agonist formoterol have been combined Budesonide and formoterol target different aspects of into a single pressurized metered-dose inhaler (pMDI). asthma pathology. [4] Budesonide has potent anti-The combination pMDI improves lung function, asthma inflammatory activity, particularly on epithelial cells in the control, asthma symptoms and asthma-related quality of airways. Formoterol, a potent, selective β2-adrenoceptor life outcomes in patients with persistent asthma that is agonist, provides rapid and long-lasting bronchodilatory mild to moderate or moderate to severe. Adapted from activity. When administered together, the effects of the Drugs 2008; 68 (13): 1865-64. [1] two agents are complementary and additive. [4] Budesonide/formoterol pMDI provides a rapid Step 2 Low-dose inhaled corticosteroid (ICS) Step 1 Inhaled short-acting β 2-adrenoceptor agonist as required for symptom relief (use at each treatment step depending on severity of symptoms) Step 4 Medium-dose ICS plus LABA Step 5 High-dose ICS plus LABA and Consider omalizumab in patients with allergies Step 6 High-dose ICS plus LABA plus oral corticosteroid and Consider omalizumab in patients with allergies Adis Data Information BV 2009 Step 3 Low-dose ICS plus inhaled long-acting β 2-adrenoceptor agonist (LABA) or Medium-dose ICS Stepwise preferred long-term management of asthma in patients aged ≥12 y. Based on US National Heart, Lung and Blood Institutes 2007 guidelines for the diagnosis and management of asthma. [2] Start treatment at the step most appropriate to asthma severity and maintain control by stepping up or down treatment when appropriate.
Journal of Asthma, Jan 20, 2020
Objective: A new epinephrine hydrofluoroalkane (HFA) asthma metered-dose inhaler (MDI) was reform... more Objective: A new epinephrine hydrofluoroalkane (HFA) asthma metered-dose inhaler (MDI) was reformulated to replace the previously marketed epinephrine chlorofluorocarbon (CFC) MDI. In addition to the HFA propellant change, several enhanced modifications (i.e. changed from solution to suspension, 43% dose reduction, etc.) were made to the formulation of epinephrine HFA MDI. This study evaluates the 6-month long-term safety and efficacy profile of the new epinephrine HFA MDI. Method: The long-term safety study consists of two 3-month, multi-center, double-or evaluator-blinded, parallel-group, placebo, and active controlled stages. In each stage, subjects aged !12 years with intermittent or mild-to-moderate persistent asthma were randomized to receive epinephrine HFA (2 Â 125 mcg/inhalation), placebo HFA, or epinephrine CFC (2 Â 220 mcg/inhalation). Bronchodilator efficacy was assessed in Stage 1 and was determined primarily by the change in the forced expiratory volume in 1 s (DFEV1) at Week 12, relative to the same day baseline. Results: The primary efficacy endpoint (AUC 0-6hrs of %DFEV1 at Week 12) for epinephrine HFA (47.3 ± 54.2) closely paralleled those for the active control, epinephrine CFC (41.0 ± 43.4). Both groups were found to be overall comparable in bronchodilator efficacy. Both also showed low incidence rates of AEs with tremor being most commonly reported for epinephrine HFA. All AEs found were non-serious and non-significant. The observed changes in vital signs, ECG, serum glucose, and potassium were minimal and not clinically relevant. Conclusion: This study demonstrated that the new epinephrine HFA is overall comparable, in both safety and efficacy, to the previous epinephrine CFC.
J Allerg Clin Immunol, 1991
American Journal of Managed Care, Sep 1, 1996
JAMA: The Journal of the American Medical Association, 1975
In Reply.— The letter of Drs Rothstein and Shapiro regarding our article, "Status Asthmaticu... more In Reply.— The letter of Drs Rothstein and Shapiro regarding our article, "Status Asthmaticus" (231:1277, 1975), makes several important points on which we wish to comment. First, we would emphasize that our remarks were directed mainly at the adult asthmatic patient. The distinction between the adult and small child is important because, as Drs Rothstein and Shapiro imply, children may be more responsive to sympathomimetic agents. Also, significant metabolic acidosis accompanying status asthmaticus is not uncommon in children, whereas it is unusual in adults. We agree that vigorous hydration and large doses of antiinflammatory corticosteroids may result in fluid retention and that caution is warranted, especially in the patient with underlying cardiac disease. Indeed, attention to daily weights and to fluid intake and output are crucial for the avoidance of overhydration and pulmonary edema. In suggesting a dosage of steroids, we were not recommending hydrocortisone necessarily as the steroid of
The Journal of family practice, 1999
Zafirlukast is an oral leukotriene receptor antagonist used in the treatment of patients with mil... more Zafirlukast is an oral leukotriene receptor antagonist used in the treatment of patients with mild to moderate asthma. To investigate its effects in a clinical practice setting, we evaluated zafirlukast in a heterogeneous group of patients who had asthma of different degrees of severity and who were receiving concomitant asthma medications. A total of 3759 patients were enrolled at 924 sites. Patients received zafirlukast 20 mg twice a day for 4 weeks. Pulmonary function was measured twice a day, and overall asthma symptom scores, number of nighttime awakenings, severity of morning asthma symptoms, and beta2-agonist use were recorded daily. In the efficacy analysis (3207 evaluable patients), all parameters showed statistically significant improvement that continued throughout the 4 weeks of the trial. A total of 71% of patients had improved pulmonary function and 72% had improved asthma symptoms. Improvement was consistent regardless of asthma severity category and regardless of con...
Current Allergy and Asthma Reports, 2007
Antileukotriene drugs have been studied for more than 15 years. In this review we examine the rol... more Antileukotriene drugs have been studied for more than 15 years. In this review we examine the role of leukotrienes in rhinitis and rhinosinusitis, and explore the clinical literature supporting the use of antileukotriene agents in these diseases. Although these medications clearly are effi cacious in rhinitis, it is unclear where in the armamentarium they should be used. The evidence for use in sinusitis has not been well studied except in sinusitis-associated aspirinexacerbated respiratory disease. In this circumstance there is information that allows use of antileukotriene agents to be considered effi cacious. We provide our rationale for use and await future clinical studies to answer this important question.
Journal of Allergy and Clinical Immunology, 1996
Journal of Allergy and Clinical Immunology, 1987
Adverse reactions to the tricyclic antidepressant drugs imipramine and desipramine have been desc... more Adverse reactions to the tricyclic antidepressant drugs imipramine and desipramine have been described and include eosinophilia, pulmonary infiltrates with eosinophilia, and elevated total serum IgE levels. The immunologic mechanism accounting for these adverse reactions has not been elucidated. This article describes a patient manifesting bronchospasm, profound eosinophilia, and elevated serum IgE levels after therapy with desipramine that resolved rapidly after withdrawal of the drug. Immunologic investigations failed to demonstrate specific IgE directed against a protein conjugate of desipramine but demonstrated the ability of desipramine to induce mast cell degranulation with direct intradermal skin challenges.
Journal of Allergy and Clinical Immunology, 2003
ceptibility haplotypes than those more exceptional patients with limited numbers of B cells who h... more ceptibility haplotypes than those more exceptional patients with limited numbers of B cells who have not, which suggests that the disease may be different between these two groups.
JAMA: The Journal of the American Medical Association, 1975
Archives of Internal Medicine, 1984
Osteoporosis International, 1993
Journal of Allergy and Clinical Immunology, 2022
Journal of Allergy and Clinical Immunology, 2016
C33. CLINICAL PROFILES AND SEVERITY OF ASTHMA, 2011