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Pagel JML, Mattos JL. Allergic Rhinitis and Its Effect on Sleep. Otolaryngol Clin North Am 2024; 57:319-328. [PMID: 37867109 DOI: 10.1016/j.otc.2023.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
Allergic rhinitis (AR) is associated with increased sleep disturbances in adults and children. Pathogenesis is multifactorial, with nasal obstruction playing a large role. Intranasal corticosteroids, antihistamines, leukotriene inhibitors, and allergen immunotherapy have been demonstrated to relieve self-reported symptoms of sleep impairment. Given the high prevalence of sleep impairment in AR, providers should consider evaluating any patient with AR for sleep disturbances and sleep-disordered breathing.
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Affiliation(s)
- Jessica M L Pagel
- University of Virginia School of Medicine, 1340 Jefferson Park Avenue, Charlottesville, VA 22903, USA
| | - Jose L Mattos
- Department of Otolaryngology-Head and Neck Surgery, University of Virginia, 1 Hospital Drive, PO Box 800713, Charlottesville, VA 22908, USA.
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2
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Wang H, Ji Q, Liao C, Tian L. A systematic review and meta-analysis of loratadine combined with montelukast for the treatment of allergic rhinitis. Front Pharmacol 2023; 14:1287320. [PMID: 37915414 PMCID: PMC10616259 DOI: 10.3389/fphar.2023.1287320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Accepted: 10/09/2023] [Indexed: 11/03/2023] Open
Abstract
Background: Loratadine and montelukast are clinical first-line drugs in the treatment of allergic rhinitis (AR). However, there is no clear evidence of the efficacy of loratadine combined with montelukast in the treatment of AR. This study aimed to evaluate the efficacy and safety of the loratadine-montelukast combination on AR. Methods: In this meta-analysis, searches were conducted on PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure (CNKI). The search terms included loratadine, montelukast, allergic rhinitis, and clinical trials. Meta-analyses were conducted using Rev Man 5.3 and Stata 15 statistical software. Results: A total of 23 studies with 4,902 participants were enrolled. For the primary outcome, pooled results showed that loratadine-montelukast can significantly reduce total nasal symptom scores (TNSS), when compared with loratadine (SMD, -1.00; 95% CI, -1.35 to -0.65, p < 0.00001), montelukast (SMD, -0.46; 95% CI, -0.68 to -0.25, p < 0.0001), or placebo (SMD, -0.93; 95% CI, -1.37 to -0.49, p < 0.00001). For secondary outcomes, pooled results showed that compared with loratadine, loratadine-montelukast can significantly improve nasal congestion, nasal itching, nasal sneezing, nasal rhinorrhea, and rhinoconjunctivitis quality of life questionnaires (RQLQ). Compared with montelukast, loratadine-montelukast can significantly improve nasal itching, and nasal sneezing. Compared with placebo, loratadine-montelukast can significantly improve nasal congestion, and RQLQ. Conclusion: Loratadine-montelukast combination is superior to loratadine monotherapy, montelukast monotherapy, or placebo in improving AR symptoms. Therefore, loratadine-montelukast combination can be an option for patients with moderate-severe AR or poorly response to monotherapy. Systematic review registration number: clinicaltrials.gov, identifier CRD42023397519.
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Affiliation(s)
- Huan Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
- Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Qing Ji
- Chengdu First People’s Hospital, Chengdu, Sichuan Province, China
| | - Chao Liao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
| | - Li Tian
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
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3
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Perez ASC, Challis JK, Ji X, Giesy JP, Brinkmann M. Impacts of wastewater effluents and seasonal trends on levels of antipsychotic pharmaceuticals in water and sediments from two cold-region rivers. THE SCIENCE OF THE TOTAL ENVIRONMENT 2022; 851:158247. [PMID: 36007655 DOI: 10.1016/j.scitotenv.2022.158247] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 08/19/2022] [Accepted: 08/19/2022] [Indexed: 06/15/2023]
Abstract
Most pharmaceuticals are found at trace concentrations in aquatic systems, but their continuous release and potential accumulation can lead to adverse health effects in exposed organisms. Concentrations can vary temporally, driven by variations in discharges of receiving waters, sorption to sediments, and other biotic and abiotic exchange processes. The principal aim of this research was to better understand the occurrence, trends, and dynamics of pharmaceuticals in a cold-climate, riverine environment. To this end, a suite of seven representative antipsychotic pharmaceuticals was measured upstream and downstream of two wastewater treatment plants (WWTPs) in Saskatchewan, Canada, located in the South Saskatchewan River and Wascana Creek, respectively, across three seasons. Concentrations of analytes were in the ng/L range and generally greater downstream of both WWTPs compared to upstream. Some compounds, including the tricyclic antidepressant amitriptyline, which was the most abundant analyte in water and sediment from both sites and across seasons, reached low μg/L concentrations. Data collected from this research effort indicate contamination with antipsychotic pharmaceuticals, with the potential to adversely impact exposed organisms.
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Affiliation(s)
- Ana Sharelys Cardenas Perez
- School of Environment and Sustainability, University of Saskatchewan, 117 Science Place Saskatoon, Saskatoon, SK S7N 5C8, Canada; Global Institute for Water Security, University of Saskatchewan, Innovation Blvd, Saskatoon, SK S7N 3H5, Canada
| | - Jonathan K Challis
- Toxicology Centre, University of Saskatchewan, 44 Campus Dr, Saskatoon, SK S7N 5B3, Canada
| | - Xiaowen Ji
- School of Environment and Sustainability, University of Saskatchewan, 117 Science Place Saskatoon, Saskatoon, SK S7N 5C8, Canada; Global Institute for Water Security, University of Saskatchewan, Innovation Blvd, Saskatoon, SK S7N 3H5, Canada
| | - John P Giesy
- Toxicology Centre, University of Saskatchewan, 44 Campus Dr, Saskatoon, SK S7N 5B3, Canada; Department of Veterinary Biomedical Sciences, University of Saskatchewan, 52 Campus Dr, Saskatoon, SK S7N 5B4, Canada; Department of Environmental Sciences, Baylor University, Waco, TX 76706, USA; Department of Zoology and Center for Integrative Toxicology, Michigan State University, 426 Auditorium Road East Lansing, MI 48824, USA
| | - Markus Brinkmann
- School of Environment and Sustainability, University of Saskatchewan, 117 Science Place Saskatoon, Saskatoon, SK S7N 5C8, Canada; Global Institute for Water Security, University of Saskatchewan, Innovation Blvd, Saskatoon, SK S7N 3H5, Canada; Toxicology Centre, University of Saskatchewan, 44 Campus Dr, Saskatoon, SK S7N 5B3, Canada; Centre for Hydrology, University of Saskatchewan, 101 - 121 Research Drive, Saskatoon, SK S7N 1K2, Canada.
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Fujii T, Kitamura Y, Kamimura S, Takeda N. Effects of sublingual immunotherapy with tablets or drops containing Japanese cedar pollen antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis. THE JOURNAL OF MEDICAL INVESTIGATION 2022; 69:97-100. [PMID: 35466153 DOI: 10.2152/jmi.69.97] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Abstract
OBJECTIVE We examined the effects of SLIT with tablets containing JCP antigens on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis during pollen dispersal season. METHODS A total of 128 patients with Japanese cedar pollinosis were categorized into four groups:19 one-year SLIT with tablets group, 16 two-year SLIT with drops group, 19 antihistamine group, and 74 untreated group. The scores of nasal symptoms and sleep disturbance were evaluated based on the Japanese guidelines for allergic rhinitis and the Athens Insomnia Scale. RESULTS The scores of nasal symptoms and sleep disturbance at the peak cedar pollen period in the two-year SLIT with drop group and the one-year SLIT with tablets group were significantly lower than those in untreated group. Additionally, these scores were significantly lower in the one-year SLIT with tablets group than those in the antihistamine group. CONCLUSION It is suggested that SLIT with JCP tablets improved both nasal symptoms and sleep disturbances at peak pollen period in patients with Japanese cedar pollinosis. SLIT with JCP tablets for one year was more effective than SLIT with JCP drops for two years and prophylactic treatment with antihistamines. J. Med. Invest. 69 : 97-100, February, 2022.
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Affiliation(s)
- Tatsuya Fujii
- Department of Otolaryngology, JA Kochi Hospital, Kochi, Japan.,Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Yoshiaki Kitamura
- Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Seiichiro Kamimura
- Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Noriaki Takeda
- Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
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Caliskan UK, Karakus MM. Evaluation of botanicals as potential COVID-19 symptoms terminator. World J Gastroenterol 2021; 27:6551-6571. [PMID: 34754152 PMCID: PMC8554406 DOI: 10.3748/wjg.v27.i39.6551] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/01/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Information about the coronavirus disease 2019 (COVID-19) pandemic is still evolving since its appearance in December 2019 and has affected the whole world. Particularly, a search for an effective and safe treatment for COVID-19 continues. Botanical mixtures contain secondary metabolites (such as flavonoids, phenolics, alkaloids, essential oils etc.) with many therapeutic effects. In this study, the use of herbal treatments against COVID-19 was evaluated. Medical synthetic drugs focus mainly on respiratory symptoms, however herbal therapy with plant extracts may be useful to relieve overall symptoms of COVID-19 due to the variety of bioactive ingredients. Since COVID-19 is a virus that affects the respiratory tract, the antiviral effects of botanicals/plants against respiratory viruses have been examined through clinical studies. Data about COVID-19 patients revealed that the virus not only affects the respiratory system but different organs including the gastrointestinal (GI) system. As GI symptoms seriously affect quality of life, herbal options that might eliminate these problems were also evaluated. Finally, computer modeling studies of plants and their active compounds on COVID-19 were included. In summary, herbal therapies were identified as potential options for both antiviral effects and control of COVID-19 symptoms. Further data will be needed to enlighten all aspects of COVID-19 pathogenesis, before determining the effects of plants on severe acute respiratory syndrome coronavirus 2.
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Affiliation(s)
- Ufuk Koca Caliskan
- Department of Pharmacognosy and Pharmaceutical Botany, Gazi University, Ankara 06500, Turkey
| | - Methiye Mancak Karakus
- Department of Pharmacognosy and Pharmaceutical Botany, Gazi University, Ankara 06500, Turkey
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Feng Y, Meng YP, Dong YY, Qiu CY, Cheng L. Management of allergic rhinitis with leukotriene receptor antagonists versus selective H1-antihistamines: a meta-analysis of current evidence. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2021; 17:62. [PMID: 34187561 PMCID: PMC8243504 DOI: 10.1186/s13223-021-00564-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Accepted: 06/14/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND Inconsistencies remain regarding the effectiveness and safety of leukotriene receptor antagonists (LTRAs) and selective H1-antihistamines (SAHs) for allergic rhinitis (AR). A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the medications. METHODS Relevant head-to-head comparative RCTs were retrieved by searching the PubMed, Embase, and Cochrane's Library databases from inception to April 20, 2020. A random-effects model was applied to pool the results. Subgroup analyses were performed for seasonal and perennial AR. RESULTS Fourteen RCTs comprising 4458 patients were included. LTRAs were inferior to SAHs in terms of the daytime nasal symptoms score (mean difference [MD]: 0.05, 95% confidence interval [CI] 0.02 to 0.08, p = 0.003, I2 = 89%) and daytime eye symptoms score (MD: 0.05, 95% CI 0.01 to 0.08, p = 0.009, I2 = 89%), but were superior in terms of the nighttime symptoms score (MD: - 0.04, 95% CI - 0.06 to - 0.02, p < 0.001, I2 = 85%). The effects of the two treatments on the composite symptom score (MD: 0.02, 95% CI - 0.02 to 0.05, p = 0.30, I2 = 91%) and rhinoconjunctivitis quality-of-life questionnaire (RQLQ) (MD: 0.01, 95% CI - 0.05 to 0.07, p = 0.71, I2 = 99%) were similar. Incidences of adverse events were comparable (odds ratio [OR]: 0.97, 95% CI 0.75 to 1.25, p = 0.98, I2 = 0%). These results were mainly obtained from studies on seasonal AR. No significant publication bias was detected. CONCLUSIONS Although both treatments are safe and effective in improving the quality of life (QoL) in AR patients, LTRAs are more effective in improving nighttime symptoms but less effective in improving daytime nasal symptoms compared to SAHs.
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Affiliation(s)
- Yan Feng
- Department of Otolaryngology-Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Otorhinolaryngology-Head and Neck Cancer, Taiyuan, China
| | - Ya-Ping Meng
- Department of Otolaryngology-Head and Neck Surgery, The First Hospital, Shanxi Medical University, Taiyuan, China
| | - Ying-Ying Dong
- Henan Vocational College of Applied Technology, Zhengzhou, China
| | - Chang-Yu Qiu
- Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China
| | - Lei Cheng
- Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
- International Centre for Allergy Research, Nanjing Medical University, Nanjing, China.
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Tan SN, Abdullah B. The Association Between Obstructive Sleep Apnea and Allergic Rhinitis: Current Literature Review. CURRENT RESPIRATORY MEDICINE REVIEWS 2021; 17:13-19. [DOI: 10.2174/1573398x17666210304100358] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/21/2021] [Accepted: 01/28/2021] [Indexed: 01/08/2023]
Abstract
:
Sleep-disordered breathing (SDB) is now a significant health problem in today's culture.
It ranges from a spectrum of abnormal conditions during sleep from the primary snorer to mild,
moderate, or severe obstructive sleep apnea (OSA). SDB also comprises other conditions, such as
sleep-related hypoventilation, sleep-related hypoxemia, and central sleep apnea syndromes.
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One of the components of the pathophysiology of OSA that remain unclear is the association of allergic
rhinitis (AR) in the evolution of OSA. Several studies relate the co-existence of OSA and
AR in the common clinical practice, but its correlation was not clear. This review article aimed to
review the pathophysiological relationship between OSA and AR in terms of the role of chemical
mediators and the effect of AR treatment in support of OSA.
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The symptoms of AR further accelerate the clinical progression to OSA development. Inflammatory
mediators such as histamine, cysteinyl leukotrienes, and interleukins are found at a high level in
AR, which can aggravate AR symptoms such as nasal obstruction, rhinorrhea, and itchiness, which
can then lead to sleep disruption in OSA patients. In addition, OSA patients also have increased
chemical mediators such as tumor necrosis factor, interleukin 6, and 1, which would activate the T
helper 2 phenotypes that can aggravate AR symptoms. This vicious cycle can potentiate each other
and worsen the condition. Few studies have shown that treatment of AR can improve OSA, especially
the use of intranasal steroid and leukotriene receptor antagonists.
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A detailed evaluation of rhinitis symptoms should be made for OSA patients so that they can benefit
not only from the improvement of AR but also the good sleep quality.
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Affiliation(s)
- Shi Nee Tan
- School of Medicine, KPJ University College, Lot PT 17010 Persiaran Seriemas, Kota Seriemas, 71800 Nilai, Negeri Sembilan, Malaysia
| | - Baharudin Abdullah
- Department of Otorhinolaryngology, Head & Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia
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Fujii T, Kitamura Y, Kamimura S, Naito K, Takeda N. Effects of sublingual immunotherapy on nasal symptoms and sleep disturbance in patients with Japanese cedar pollinosis. Auris Nasus Larynx 2021; 48:653-658. [PMID: 33461852 DOI: 10.1016/j.anl.2021.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 12/23/2020] [Accepted: 01/04/2021] [Indexed: 10/22/2022]
Abstract
OBJECTIVE Japanese cedar (JC) pollinosis is the most common seasonal allergic rhinitis (AR) in Japan. AR reduces the quality of life not only because of nasal symptoms but also because of sleep disturbance. In the present study, we investigated the effects of sublingual immunotherapy (SLIT) with a standardized JC pollen extract on nasal symptoms and AR-related sleep disturbance in patients with JC pollinosis. METHODS In the present non-randomized controlled study, we assigned thirty-one patients with JC pollinosis who received SLIT into the SLIT group, and another thirty-eight patients with JC pollinosis who visited our hospital without treatment into the untreated group. We evaluated nasal symptoms and sleep disturbance using the classification of the severity of AR symptoms and the Athens Insomnia Scale, respectively. RESULTS The nasal symptom scores and the Athens Insomnia Scale scores of patients in the SLIT group were both significantly lower than those of patients in the untreated group. There was a significant correlation between total nasal symptom scores and the Athens Insomnia Scale scores. CONCLUSIONS These findings suggested that SLIT with JC pollen extract suppressed nasal symptoms in patients with JC pollinosis, leading to improvements in AR-related sleep disturbance and daytime troubles with daily life.
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Affiliation(s)
- Tatsuya Fujii
- Department of Otolaryngology, JA Kochi Hospital, Kochi 783-8509, Japan; Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
| | - Yoshiaki Kitamura
- Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
| | - Seiichiro Kamimura
- Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
| | - Keisuke Naito
- Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
| | - Noriaki Takeda
- Department of Otolaryngology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
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Krishnamoorthy M, Mohd Noor N, Mat Lazim N, Abdullah B. Efficacy of Montelukast in Allergic Rhinitis Treatment: A Systematic Review and Meta-Analysis. Drugs 2020; 80:1831-1851. [PMID: 32915441 DOI: 10.1007/s40265-020-01406-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND In treating allergic rhinitis, montelukast has the potential to be used as an alternative or addition to an oral antihistamine or intranasal corticosteroid. OBJECTIVE The objective of this systematic review was to assess the effectiveness of montelukast in treating allergic rhinitis. METHODS An electronic literature search was performed using the Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE from 1966 to 21 January 2019. The eligibility criteria were randomized controlled trials comparing montelukast with placebo or other standard treatments. The primary outcomes assessed were daytime nasal symptom score (DNS) and night-time nasal symptom score (NNS). The secondary outcomes assessed were composite nasal symptom score (CSS), daytime eyes symptom score (DES), and rhinoconjunctivitis quality-of-life questionnaires (RQLQ). The meta-analysis was conducted using Review Manager 5.3 software based on the random-effects model. RESULTS Fifteen studies of 10387 participants met the inclusion criteria. Montelukast was more effective than placebo in improving DNS (mean difference [MD] - 0.12, 95% confidence interval [CI] - 0.15 to - 0.08; p < 0.001), NNS (MD - 0.09, 95% CI - 0.13 to - 0.05; p < 0.001), CSS (MD - 0.08, 95% CI - 0.11 to - 0.06; p < 0.001), DES (MD - 0.17, 95% CI - 0.33 to - 0.02; p < 0.030), and RQLQ (MD - 0.34, 95% CI - 0.49 to - 0.20; p < 0.001). Oral antihistamine was superior to montelukast in improving DNS (MD 0.08, 95% CI 0.03-0.13; p = 0.002), CSS (MD 0.03, 95% CI - 0.02 to 0.07; p = 0.27), DES (MD 0.06, 95% CI 0-0.12; p = 0.040), and RQLQ (MD 0.03, 95% CI - 0.05 to 0.12; p = 0.430). Montelukast was superior to oral antihistamine in improving NNS (MD -0.03, 95% CI - 0.08 to 0.03; p = 0.330). Intranasal fluticasone spray was superior to montelukast in improving DNS (MD 0.71, 95% CI 0.44-0.99; p < 0.001) and NNS (MD 0.63, 95% CI 0.29-0.97; p < 0.001). Combined montelukast and oral antihistamine was superior to oral antihistamine in improving DNS (MD - 0.15, 95% CI - 0.27 to - 0.03; p = 0.010), NNS (MD - 0.16, 95% CI - 0.28 to - 0.05; p = 0.006), CSS (MD - 0.12, 95% CI - 0.25 to - 0.01; p = 0.070), DES (MD - 0.12, 95% CI - 0.30 to 0.06; p = 0.180), and RQLQ (MD - 0.10, 95% CI - 0.28 to 0.08; p = 0.290). Combined montelukast and OAH was superior to montelukast in improving DNS (MD 0.15, 95% CI 0.08-0.21; p < 0.001), NNS (MD 0.05, 95% CI - 0.09 to 0.19; p = 0.510), CSS (MD 0.1, 95% CI 0.03-0.17; p = 0.007), DES (MD 0.18, 95% CI 0-0.36; p = 0.050), and RQLQ (MD 0.07 95% CI - 0.15 to 0.29; p = 0.530). CONCLUSIONS Montelukast is more effective than placebo in treating the overall symptoms of allergic rhinitis while the combined therapy of montelukast and an oral antihistamine is superior to either montelukast or an oral antihistamine alone.
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Affiliation(s)
- Madhusudhan Krishnamoorthy
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Norhayati Mohd Noor
- Department of Family Medicine, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Norhafiza Mat Lazim
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia
| | - Baharudin Abdullah
- Department of Otorhinolaryngology-Head and Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.
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Marcuccio G, DI Bari MM, Precenzano F, Operto FF, Bitetti I, Motta G, Testa D. Relationship between sleep quality and rhinitis in children: role of medical treatment with isotonic and hypertonic saline. Minerva Pediatr (Torino) 2019; 73:301-306. [PMID: 31352769 DOI: 10.23736/s2724-5276.19.05563-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
BACKGROUND The nose represents the port of entry, the first part of the upper airway and accounts for 50% of its total resistance. Many authors identified rhinitis as relevant factor affecting quality of life, and sleep habits of sufferers and their caregiver's, particularly between 4-17 years old children. Both allergic rhinitis and non-allergic rhinitis may represent an important risk for obstructive sleep apnea syndrome in children. We evaluated the quality of sleep and the role of nasal irrigations with saline solutions in children with sign and symptoms of rhinitis. METHODS An observational retrospective study was conducted on 58 children aged 3-6 years old receiving diagnosis of rhinitis according to clinical and amnestic evaluation. All recruited children were screened before medical topic treatment with the Pediatric Sleep Questionnaire test in order to evaluate the sleep habits and after isotonic and hypertonic saline nasal irrigation for six months. One-Way ANOVA was used for statistical analysis of the results. RESULTS Forty-nine of 58 recruited children reached the follow-up control after six months of medical treatment. Mean score at Pediatric Sleep Questionnaire before and after medical treatments was respectively 0.39 and 0.28. One-Way ANOVA test showed a significant statistical difference (P<0.05). CONCLUSIONS Nasal topic decongestant may be used only for short-term treatments, and they do not seem to have long-term results. Topic corticosteroids may be used for long term treatment and their correlations with OSA seem to have different results. This study aims to attracting the attention of pediatricians on the importance of nasal topic saline solutions irrigations in children with rhinitis in improving HRQoL decreasing snoring and apneas and so daytime symptoms.
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Affiliation(s)
- Giuseppina Marcuccio
- Unit of Head and Neck Surgery, Division of Otorhinolaryngology, Department of Mental and Physical Health and Preventive Medicine, Luigi Vanvitelli University of Campania, Naples, Italy -
| | - Matteo Matteo DI Bari
- Unit of Head and Neck Surgery, Division of Otorhinolaryngology, Department of Mental and Physical Health and Preventive Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Francesco Precenzano
- Unit of Child and Adolescent Neuropsychiatry, Department of Mental and Physical Health and Preventive Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Francesca F Operto
- Unit of Child Neuropsychiatry, Department of Basic Medical Sciences, Neuroscience and Sense Organs, Aldo Moro University, Bari, Italy
| | - Ilaria Bitetti
- Unit of Child and Adolescent Neuropsychiatry, Department of Mental and Physical Health and Preventive Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Gaetano Motta
- Unit of Head and Neck Surgery, Division of Otorhinolaryngology, Department of Mental and Physical Health and Preventive Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
| | - Domenico Testa
- Unit of Head and Neck Surgery, Division of Otorhinolaryngology, Department of Mental and Physical Health and Preventive Medicine, Luigi Vanvitelli University of Campania, Naples, Italy
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11
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Scadding GK, Kariyawasam HH, Scadding G, Mirakian R, Buckley RJ, Dixon T, Durham SR, Farooque S, Jones N, Leech S, Nasser SM, Powell R, Roberts G, Rotiroti G, Simpson A, Smith H, Clark AT. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007). Clin Exp Allergy 2019; 47:856-889. [PMID: 30239057 DOI: 10.1111/cea.12953] [Citation(s) in RCA: 163] [Impact Index Per Article: 27.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Revised: 05/01/2017] [Accepted: 05/04/2017] [Indexed: 12/12/2022]
Abstract
This is an updated guideline for the diagnosis and management of allergic and non-allergic rhinitis, first published in 2007. It was produced by the Standards of Care Committee of the British Society of Allergy and Clinical Immunology, using accredited methods. Allergic rhinitis is common and affects 10-15% of children and 26% of adults in the UK, it affects quality of life, school and work attendance, and is a risk factor for development of asthma. Allergic rhinitis is diagnosed by history and examination, supported by specific allergy tests. Topical nasal corticosteroids are the treatment of choice for moderate to severe disease. Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more effective than either alone and provides second line treatment for those with rhinitis poorly controlled on monotherapy. Immunotherapy is highly effective when the specific allergen is the responsible driver for the symptoms. Treatment of rhinitis is associated with benefits for asthma. Non-allergic rhinitis also is a risk factor for the development of asthma and may be eosinophilic and steroid-responsive or neurogenic and non- inflammatory. Non-allergic rhinitis may be a presenting complaint for systemic disorders such as granulomatous or eosinophilic polyangiitis, and sarcoidoisis. Infective rhinitis can be caused by viruses, and less commonly by bacteria, fungi and protozoa.
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Affiliation(s)
- G K Scadding
- The Royal National Throat Nose and Ear Hospital, London, UK
| | - H H Kariyawasam
- The Royal National Throat Nose and Ear Hospital, London, UK.,UCLH NHS Foundation Trust, London, UK
| | - G Scadding
- Department of Upper Respiratory Medicine, Imperial College NHLI, London, UK
| | - R Mirakian
- The Royal National Throat Nose and Ear Hospital, London, UK
| | - R J Buckley
- Vision and Eye Research Unit, Anglia Ruskin University, Cambridge, UK
| | - T Dixon
- Royal Liverpool and Broad green University Hospital NHS Trust, Liverpool, UK
| | - S R Durham
- Department of Upper Respiratory Medicine, Imperial College NHLI, London, UK
| | - S Farooque
- Chest and Allergy Department, St Mary's Hospital, Imperial College NHS Trust, London, UK
| | - N Jones
- The Park Hospital, Nottingham, UK
| | - S Leech
- Department of Child Health, King's College Hospital, London, UK
| | - S M Nasser
- Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
| | - R Powell
- Department of Clinical Immunology and Allergy, Nottingham University, Nottingham UK
| | - G Roberts
- Department of Child Health, University of Southampton Hospital, Southampton, UK
| | - G Rotiroti
- The Royal National Throat Nose and Ear Hospital, London, UK
| | - A Simpson
- Division of Infection, Immunity and Respiratory Medicine, University of Manchester, UK
| | - H Smith
- Division of Primary Care and Public Health, University of Sussex, Brighton, UK
| | - A T Clark
- Cambridge University Hospital NHS Foundation Trust, Cambridge, UK
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12
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Raynor DK, Myers L, Blackwell K, Kress B, Dubost A, Joos A. Clinical Trial Results Summary for Laypersons: A User Testing Study. Ther Innov Regul Sci 2018; 52:606-628. [DOI: 10.1177/2168479017753129] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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13
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Hashiguchi K, Okubo K, Inoue Y, Numaguchi H, Tanaka K, Oshima N, Mehta A, Nishida C, Saito I, Philip G. Evaluation of Montelukast for the Treatment of Children With Japanese Cedar Pollinosis Using an Artificial Exposure Chamber (OHIO Chamber). ALLERGY & RHINOLOGY 2018; 9:2152656718783599. [PMID: 30027002 PMCID: PMC6047236 DOI: 10.1177/2152656718783599] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background This study evaluated the efficacy of montelukast in reducing seasonal
allergic rhinitis symptoms in Japanese children with Japanese cedar (JC)
pollinosis induced in an artificial exposure chamber (OHIO Chamber). Methods Pediatric patients aged 10 to 15 years sensitive to JC pollen entered a
randomized, double-blind, single-site, crossover study. After confirmation
of an allergic response to a JC pollen exposure for 3 hours in the OHIO
Chamber during the screening period, subjects received either montelukast 5
mg chewable tablets or placebo for a 7-day treatment period, followed by a
3-hour pollen exposure in the chamber. After a 7-day washout period,
subjects crossed over to the other treatment. Subjects were instructed to
self-assess their nasal symptoms using 5-point scale for every 30 minutes.
The primary end point was the change from baseline (just before entering the
exposure chamber for each exposure) in total nasal symptom score (TNSS; the
sum of nasal congestion, nasal discharge, and sneezing scores) over 3 hours
of pollen exposure. Adverse events (AEs) were evaluated throughout the
study. Results A total of 220 subjects (median age, 12 years) received treatment. For TNSS,
the between-group difference in the change (95% confidence interval) was
−0.01 (−0.11 to 0.10); the change between placebo and montelukast 5 mg was
not significant. TNSS in the screening and treatment periods after receiving
placebo for 7 days was 1.58 and 1.31, respectively, suggesting a placebo
response. On account of high placebo response, a post hoc analysis was
conducted. The analysis in a subgroup of subjects who did not show placebo
response demonstrated a difference in the efficacy between montelukast and
placebo (nominal P < .037). The most common AE was
positive urine protein (4.6% with montelukast vs 7.8% with placebo). Conclusions Although montelukast was well tolerated, this study did not demonstrate a
treatment difference between active drug and placebo in Japanese children
exposed to JC pollen in the OHIO Chamber. Trial Registry: ClinicalTrials.gov, NCT01852812
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Affiliation(s)
- Kazuhiro Hashiguchi
- Department of Otorhinolaryngology, Futaba Clinic, Tokyo, Japan.,Medical Corporation Shinanokai, Samoncho Clinic, Tokyo, Japan
| | - Kimihiro Okubo
- Department of Otorhinolaryngology, Nippon Medical School Hospital, Tokyo, Japan
| | | | | | | | | | - Anish Mehta
- Merck & Co., Inc., Kenilworth, New Jersey, USA
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14
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Kim MK, Lee SY, Park HS, Yoon HJ, Kim SH, Cho YJ, Yoo KH, Lee SK, Kim HK, Park JW, Park HW, Chung JH, Choi BW, Lee BJ, Chang YS, Jo EJ, Lee SY, Cho YS, Jee YK, Lee JM, Jung J, Park CS. A Randomized, Multicenter, Double-blind, Phase III Study to Evaluate the Efficacy on Allergic Rhinitis and Safety of a Combination Therapy of Montelukast and Levocetirizine in Patients With Asthma and Allergic Rhinitis. Clin Ther 2018; 40:1096-1107.e1. [PMID: 29945738 DOI: 10.1016/j.clinthera.2018.04.021] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 04/25/2018] [Accepted: 04/30/2018] [Indexed: 12/30/2022]
Abstract
PURPOSE The aim of this study was to evaluate the efficacy and safety of a fixed-dose combination of montelukast and levocetirizine in patients with perennial allergic rhinitis with mild to moderate asthma compared with the efficacy and safety of montelukast alone. METHODS This study was a 4-week, randomized, multicenter, double-blind, Phase III trial. After a 1-week placebo run-in period, the subjects were randomized to receive montelukast (10 mg/day, n = 112) or montelukast (10 mg/day)/levocetirizine (5 mg/day) (n = 116) treatment for 4 weeks. The primary efficacy end point was mean daytime nasal symptom score. Other efficacy end points included mean nighttime nasal symptom score, mean composite symptom score, overall assessment of allergic rhinitis by both subjects and physicians, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, asthma control test score, and the frequency of rescue medication used during the treatment period. FINDINGS Of 333 patients screened for this study, 228 eligible patients were randomized to treatment. The mean (SD) age of patients was 43.32 (15.02) years, and two thirds of subjects were female (66.67%). The demographic characteristics were similar between the treatment groups. Compared with the montelukast group, the montelukast/levocetirizine group reported significant reductions in mean daytime nasal symptom score (least squares mean [SE] of combination vs montelukast, -0.98 [0.06] vs -0.81 [0.06]; P = 0.045). For all other allergic rhinitis efficacy end points, the montelukast/levocetirizine group showed greater improvement than the montelukast group. Similar results were observed in overall assessment scores and in FEV1, FVC, FEV1/FVC, and asthma control test score changes from baseline for the 2 treatment groups. Montelukast/levocetirizine was well tolerated, and the safety profile was similar to that observed in the montelukast group. IMPLICATIONS The fixed-dose combination of montelukast and levocetirizine was effective and safe in treating perennial allergic rhinitis in patients with asthma compared with montelukast alone. ClinicalTrials.gov identifier: NCT02552667.
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Affiliation(s)
- Mi-Kyeong Kim
- Subdivision of Allergy, Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Republic of Korea
| | - Sook Young Lee
- Division of Allergy, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hae-Sim Park
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Ho Joo Yoon
- Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Republic of Korea
| | - Sang-Ha Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Young Joo Cho
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Republic of Korea
| | - Kwang-Ha Yoo
- Pulmonary-Allergy Division, Department of Internal Medicine, Konkuk University College of Medicine, Seoul, Republic of Korea
| | - Soo-Keol Lee
- Department of Internal Medicine, College of Medicine, Dong-A University, Busan, Republic of Korea
| | - Hee-Kyoo Kim
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Republic of Korea
| | - Jung-Won Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Heung-Woo Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin-Hong Chung
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Byoung Whui Choi
- Division of Respirology and Allergy, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea
| | - Byung-Jae Lee
- Division of Allergy, Department of Medicine, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Republic of Korea
| | - Yoon-Seok Chang
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Eun-Jung Jo
- Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Pusan National University College of Medicine, Busan, Republic of Korea
| | - Sang-Yeub Lee
- Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - You Sook Cho
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Young-Koo Jee
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea
| | - Jong-Myung Lee
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Jina Jung
- Hanmi Pharmaceutical Co, Seoul, Republic of Korea
| | - Choon-Sik Park
- Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea.
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15
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Chin WK, Lee SWH. A systematic review on the off-label use of montelukast in atopic dermatitis treatment. Int J Clin Pharm 2018; 40:963-976. [DOI: 10.1007/s11096-018-0655-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Accepted: 05/08/2018] [Indexed: 12/01/2022]
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16
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Meltzer EO, Philip G, Weinstein SF, LaForce CF, Malice MP, Dass SB, Santanello NC, Reiss TF. Montelukast Effectively Treats the Nighttime Impact of Seasonal Allergic Rhinitis. ACTA ACUST UNITED AC 2018. [DOI: 10.1177/194589240501900611] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Background Nighttime problems constitute a significant burden on the quality of life of patients with seasonal allergic rhinitis (SAR). The aim of this study was to evaluate the effectiveness of montelukast on nighttime AR symptoms. Methods In seven multicenter, double-blind, parallel-group trials, nighttime problems were assessed as the nighttime symptoms score (NSS), an average of three individual symptom scores: difficulty going to sleep, nighttime awakening, and nasal congestion on awakening (each rated 0 = none to 3 = severe). Patients (aged 15–82 years) were randomized to receive montelukast, 10 mg (n = 1751), placebo (n = 1557), or the positive control loratadine, 10 mg (n = 1616). Results In a combined analysis, changes from baseline (mean ± SE) in NSS were -0.28 ± 0.01, -0.16 ± 0.01, and —0.24 ± 0.01 for the montelukast, placebo, and loratadine groups, respectively. Difference versus placebo in least-squares mean change from baseline were —0.11 (95% confidence interval, -0.14, -0.08; p ≤ 0.001) for montelukast and -0.09 (-0.12, -0.06; p ≤ 0.001) for loratadine. Strong baseline correlations (R > 0.70; p < 0.001) of NSS and two of its individual symptoms with the sleep domain of the validated Rhinoconjunctivitis Quality of Life Questionnaire support the validity and importance of measuring nighttime morbidity in SAR. Furthermore, a clinically important benefit of montelukast on the nighttime impact of SAR was shown using an analysis anchored on the Patient's Global Evaluation. Conclusion These data underscore the importance of nighttime problems in patients with SAR and the need to treat nighttime symptoms. In these studies, montelukast significantly improved the NSS, a clinically relevant and valid measure in patients with SAR.
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Affiliation(s)
- Eli O. Meltzer
- Allergy and Asthma Medical Group and Research Center, A.P.C., San Diego, California
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17
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Wise SK, Lin SY, Toskala E, Orlandi RR, Akdis CA, Alt JA, Azar A, Baroody FM, Bachert C, Canonica GW, Chacko T, Cingi C, Ciprandi G, Corey J, Cox LS, Creticos PS, Custovic A, Damask C, DeConde A, DelGaudio JM, Ebert CS, Eloy JA, Flanagan CE, Fokkens WJ, Franzese C, Gosepath J, Halderman A, Hamilton RG, Hoffman HJ, Hohlfeld JM, Houser SM, Hwang PH, Incorvaia C, Jarvis D, Khalid AN, Kilpeläinen M, Kingdom TT, Krouse H, Larenas-Linnemann D, Laury AM, Lee SE, Levy JM, Luong AU, Marple BF, McCoul ED, McMains KC, Melén E, Mims JW, Moscato G, Mullol J, Nelson HS, Patadia M, Pawankar R, Pfaar O, Platt MP, Reisacher W, Rondón C, Rudmik L, Ryan M, Sastre J, Schlosser RJ, Settipane RA, Sharma HP, Sheikh A, Smith TL, Tantilipikorn P, Tversky JR, Veling MC, Wang DY, Westman M, Wickman M, Zacharek M. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol 2018; 8:108-352. [PMID: 29438602 PMCID: PMC7286723 DOI: 10.1002/alr.22073] [Citation(s) in RCA: 240] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 12/01/2017] [Accepted: 12/01/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.
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Affiliation(s)
| | | | | | | | - Cezmi A. Akdis
- Allergy/Asthma, Swiss Institute of Allergy and Asthma Research, Switzerland
| | | | - Antoine Azar
- Allergy/Immunology, Johns Hopkins University, USA
| | | | | | | | | | - Cemal Cingi
- Otolaryngology, Eskisehir Osmangazi University, Turkey
| | | | | | | | | | | | | | - Adam DeConde
- Otolaryngology, University of California San Diego, USA
| | | | | | | | | | | | | | - Jan Gosepath
- Otorhinolaryngology, Helios Kliniken Wiesbaden, Germany
| | | | | | | | - Jens M. Hohlfeld
- Respiratory Medicine, Hannover Medical School, Airway Research Fraunhofer Institute for Toxicology and Experimental Medicine, German Center for Lung Research, Germany
| | | | | | | | | | | | | | | | | | | | | | | | | | - Amber U. Luong
- Otolaryngology, McGovern Medical School at the University of Texas Health Science Center Houston, USA
| | | | | | | | - Erik Melén
- Pediatric Allergy, Karolinska Institutet, Sweden
| | | | | | - Joaquim Mullol
- Otolaryngology, Universitat de Barcelona, Hospital Clinic, IDIBAPS, Spain
| | | | | | | | - Oliver Pfaar
- Rhinology/Allergy, Medical Faculty Mannheim, Heidelberg University, Center for Rhinology and Allergology, Wiesbaden, Germany
| | | | | | - Carmen Rondón
- Allergy, Regional University Hospital of Málaga, Spain
| | - Luke Rudmik
- Otolaryngology, University of Calgary, Canada
| | - Matthew Ryan
- Otolaryngology, University of Texas Southwestern, USA
| | - Joaquin Sastre
- Allergology, Hospital Universitario Fundacion Jiminez Diaz, Spain
| | | | | | - Hemant P. Sharma
- Allergy/Immunology, Children's National Health System, George Washington University School of Medicine, USA
| | | | | | | | | | | | - De Yun Wang
- Otolaryngology, National University of Singapore, Singapore
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Liu G, Zhou X, Chen J, Liu F. Oral Antihistamines Alone vs in Combination with Leukotriene Receptor Antagonists for Allergic Rhinitis: A Meta-analysis. Otolaryngol Head Neck Surg 2018; 158:450-458. [PMID: 29337654 DOI: 10.1177/0194599817752624] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Objective To evaluate whether an adjuvant therapy of leukotriene receptor antagonists (LTRAs) based on oral H1-antihistamines (H1) can increase efficacy of allergic rhinitis (AR) treatment. Data Sources The search involved databases of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, from inception up to September 23, 2017. Randomized controlled trials (RCTs) that compared efficacy of LTRAs + H1 vs H1 alone were eligible. Review Methods Pooled comparative effects were measured using weighted mean difference (WMD) and 95% confidence interval (CI). Subgroup analysis comparing seasonal vs perennial AR was prespecified to explore the source of heterogeneity. The evidence quality of each outcome was assessed by the GRADE approach. Results A total of 8 RCTs were included (n = 1886), and all measured outcomes used scaled scores. Compared with H1 alone, H1 + LTRAs were superior to improve overall daytime (WMD, -0.11; 95% CI, -0.19 to -0.03, high quality) and composite (WMD, -0.12; 95% CI, -0.23 to -0.01; low quality) nasal symptoms. Specifically, H1 + LTRAs had better efficacy against composite nasal rhinorrhea, sneezing, and daytime itching but not congestion. The effects were more pronounced in patients with perennial AR compared to those with seasonal AR. There were no significant differences in nighttime nasal symptoms and eye symptoms between the 2 groups. Conclusion The current evidence suggests that LTRAs + H1 can increase the therapeutic efficacy against daytime and composite nasal symptoms, including rhinorrhea, sneezing, and itching; however, it does not affect nighttime nasal symptoms and eye symptoms. The patients with perennial AR may benefit more from the combination therapy.
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Affiliation(s)
- Guo Liu
- 1 Department of Otolaryngology-Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xu Zhou
- 2 Evidence-based Medicine Research Center, School of Basic Medical Sciences, Jiangxi University of Traditional Chinese Medicine, Jiangxi, China
| | - Jianrong Chen
- 3 Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Feng Liu
- 1 Department of Otolaryngology-Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, China
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19
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Chin WK. Leukotriene receptor antagonism may not be effective in atopic dermatitis treatment after all. J Clin Pharm Ther 2017; 43:159-162. [DOI: 10.1111/jcpt.12648] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2017] [Accepted: 10/05/2017] [Indexed: 11/26/2022]
Affiliation(s)
- W. K. Chin
- School of Pharmacy; Monash University Malaysia; Subang Jaya Malaysia
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Okubo K, Inoue Y, Numaguchi H, Tanaka K, Saito I, Oshima N, Matsumoto Y, Prohn M, Mehta A, Nishida C, Philip G. Montelukast in the treatment of perennial allergic rhinitis in paediatric Japanese patients; an open-label clinical trial. J Drug Assess 2016; 5:6-14. [PMID: 27785374 PMCID: PMC5040008 DOI: 10.1080/21556660.2016.1209507] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 06/30/2016] [Accepted: 07/01/2016] [Indexed: 11/04/2022] Open
Abstract
Background: This study was conducted to evaluate the safety and tolerability, and population pharmacokinetics (PPK) of montelukast as well as efficacy in the treatment of perennial allergic rhinitis (PAR) in paediatric Japanese patients aged between 1 and 15 years. Methods: In this multi-centre, open-label trial, 87 paediatric Japanese patients with PAR received montelukast 4 mg oral granules (OG) for 4 weeks (1-5-year-olds, N = 15), 4 mg OG for 12 weeks (1-5-year-olds, N = 36), 5 mg chewable tablets (CT) for 12 weeks (6-9-year-olds, N = 18), or 5 mg CT for12 weeks (10-15-year-olds, N = 18). Clinical exams and laboratory assessments were conducted at study visits, and adverse events (AE) were monitored throughout the study up to 14 days after the last visit. Population pharmacokinetic approach was used to estimate AUC0-∞, Cmax, Tmax and apparent elimination half-life in each age group. Efficacy was assessed based on global evaluations by the subject's caregiver. Results: There were no serious AEs and one discontinuation due to an AE. The most common AEs in any of the treatment groups were nasopharyngitis, pharyngitis, and acute sinusitis. Montelukast exposure (AUC0-∞) was similar in the 1-5-year-old group and the 6-9-year-old group, but 19% lower in the 10-15-year-old group. Among all patients, the total proportion of patients whose global evaluation was "very much better" was 5.7% (week 2), 11.5% (week 4), and 16.9% (week 12) reflecting improvement in symptoms over time. Conclusion: Montelukast was generally well tolerated in Japanese children with PAR. AUC0-∞was similar in 1-5 and 6-9-year-olds, while a lower exposure was observed in the 10-15-year-old group likely due to differences in bodyweight. The exposure in Japanese paediatric patients was generally consistent with that in non-Japanese paediatric and adult patients. As assessed by the patients' caregivers, montelukast also demonstrated symptomatic improvement based on global evaluations of PAR.
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Affiliation(s)
- Kimihiro Okubo
- Department of Otorhinolaryngology, Nippon Medical School Hospital,
Tokyo,
Japan
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21
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The efficacy and safety of H1-antihistamine versus Montelukast for allergic rhinitis: A systematic review and meta-analysis. Biomed Pharmacother 2016; 83:989-997. [PMID: 27522261 DOI: 10.1016/j.biopha.2016.08.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 07/28/2016] [Accepted: 08/01/2016] [Indexed: 02/07/2023] Open
Abstract
PURPOSE In order to verify the differences of effectiveness and safety between SAHs and Montelukast, and to find out potential uncared-for problems, we performed a systematic review and Meta-analysis to proceed a qualitative describe and quantitative assessment. METHODS We searched the databases of Pubmed, the Cochrane Library, Nature and Science as well as Wanfang data and CNKI from 2000 to March 2016, using key words "Montelukast SAH" or "H1-antihistamine Montelukast", or "Loratadine Montelukast", or "Desloratadine Montelukast", or "Levocetirizine Montelukast", or "Cetirizen Montelukast", or "Fexofenadine Montelukast". And also we included studies through relevant citations in related literature. Meta-analysis and bias of risk were performed. We analyzed Heterogeneity and publish bias as well. RESULT Montelukast seems more effective in nighttime symptoms compare with SAHs (P=0.008, MD=-0.04, 95%CI: -0.08, -0.01). No significant difference was found between Montelukast and SAHs in CSS (P=0.10, MD=0.03, 95%CI: -0.01, 0.07). Montelukast and SAHs combined therapy was more effective than Montelukast DNSS (P=0.0006, MD=0.15, 95%CI: 0.07, 0.24) but not in CSS (P=0.04, MD=0.08, 95%CI: 0.00, 0.15; Bonferroni correction α=0.017). CONCLUSION Montelukast has a significant influence in improving patients' nasal symptoms quality of live but is not as effective as SAHs, and may have a slight advantage over SAHs in relieving nighttime symptoms significantly. Combined therapy is more effective in improving patients' day time symptom than Montelukast. Probably, patients might have a lower asthenia incidence rate when using Montelukas.
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Durham SR, Creticos PS, Nelson HS, Li Z, Kaur A, Meltzer EO, Nolte H. Treatment effect of sublingual immunotherapy tablets and pharmacotherapies for seasonal and perennial allergic rhinitis: Pooled analyses. J Allergy Clin Immunol 2016; 138:1081-1088.e4. [PMID: 27527264 DOI: 10.1016/j.jaci.2016.04.061] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Revised: 04/18/2016] [Accepted: 04/29/2016] [Indexed: 01/08/2023]
Abstract
BACKGROUND Data comparing the treatment effect of allergy immunotherapy and pharmacotherapy are lacking. OBJECTIVE We sought to indirectly compare the treatment effect of sublingual immunotherapy (SLIT)-tablets with pharmacotherapy for seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR). METHODS Pooled data from randomized, double-blind, placebo-controlled trials for the clinical development programs of selected allergic rhinitis treatments were evaluated. Total nasal symptom scores (TNSSs) relative to placebo were compared. Subjects scored symptoms daily during entire pollen seasons in 6 timothy grass SLIT-tablet trials (n = 3094) and 2 ragweed SLIT-tablet trials (n = 658) and during the last 8 weeks of treatment in 2 house dust mite (HDM) SLIT-tablet trials (n = 1768). Subjects scored symptoms daily in 7 montelukast (10 mg, n = 6799), 9 desloratadine (5 mg, n = 4455), and 8 mometasone furoate nasal spray (MFNS; 200 μg daily, n = 2140) SAR or PAR trials. SLIT-tablet trials allowed rescue medication use, whereas most pharmacotherapy trials did not. A fixed-effect meta-analysis method estimated differences in on-treatment average TNSSs. RESULTS In grass and ragweed SLIT-tablet trials, overall improvement in TNSSs relative to placebo was 16.3% and 17.1%, respectively. In HDM SLIT-tablet trials, TNSS overall improvement relative to placebo was 16.1%. In the montelukast, desloratadine, and MFNS trials, TNSS overall improvement relative to placebo was 5.4%, 8.5%, and 22.2%, respectively, for SAR trials, and 3.7%, 4.8%, and 11.2%, respectively, for PAR trials. CONCLUSIONS Although comparisons were limited by study design heterogeneity and use of rescue medications in SLIT-tablet trials, effects on nasal symptoms with timothy grass and ragweed SLIT-tablets were nearly as great as with MFNS and numerically greater than with montelukast and desloratadine for SAR. HDM SLIT-tablet effects were numerically greater than all pharmacotherapies for PAR. SLIT-tablets offer the additional benefit of long-term efficacy.
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Affiliation(s)
- Stephen R Durham
- Royal Brompton and Harefield Hospitals National Health Service Trust and Imperial College, London, United Kingdom
| | - Peter S Creticos
- Creticos Research Group and Division of Allergy & Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md
| | | | | | | | - Eli O Meltzer
- Allergy & Asthma Medical Group & Research Center, San Diego, Calif
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Krouse JH, Roland PS, Marple BF, Wall GM, Hannley M, Golla S, Hunsaker D. Optimal Duration of Allergic Rhinitis Clinical Trials. Otolaryngol Head Neck Surg 2016; 133:467-87; discussion 488. [PMID: 16213915 DOI: 10.1016/j.otohns.2005.07.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2005] [Accepted: 07/19/2005] [Indexed: 11/16/2022]
Abstract
OBJECTIVE: Guidelines have been published by the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA) for the conduct of seasonal allergic rhinitis (SAR) and perennial allergic rhinitis (PAR) studies. These guidelines have differences regarding the duration of such trials: the FDA suggests 2 weeks for SAR and 4 weeks for PAR but the EMEA suggests 2 to 4 weeks for SAR and 6 to 12 weeks for PAR trials. In the interest of global harmonization, it would be desirable to have a uniform duration of such trials so that investigators, internationally, would be able to readily compare results for various types of treatments based on a single standard. Therefore, we performed an evidence-based review to answer the clinical question, What is the optimal duration for SAR and PAR clinical trials? METHODS: We performed a MEDLINE search of the published literature from 1995 to the present. We used appropriate search terms, such as allergic rhinitis, seasonal allergic rhinitis, perennial allergic rhinitis, SAR, and PAR, to identify pertinent articles. These articles were reviewed and graded according to the evidence quality. RESULTS: After an initial screening of more than 300 articles, 138 articles were analyzed thoroughly. No study specifically addressed the question of the optimal duration of SAR or PAR clinical trials. CONCLUSIONS: We conclude that the current FDA (draft) guidelines calling for a study length of 2 weeks for the assessment of drug efficacy for SAR and 4 weeks for the study of drug efficacy in PAR are appropriate and that longer study periods are not likely to add meaningfully to the assessment of drug efficacy.
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Affiliation(s)
- John H Krouse
- Department of Otolaryngology-Head and Neck Surgery, Wayne State University, Detroit, MI 48201, USA.
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Erdem SB, Nacaroglu HT, Unsal Karkiner CS, Gunay I, Can D. Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children. IRANIAN JOURNAL OF PEDIATRICS 2015; 25:e3313. [PMID: 26495098 PMCID: PMC4610338 DOI: 10.5812/ijp.3313] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 08/16/2015] [Indexed: 11/30/2022]
Abstract
Background: Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. Objectives: The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. Patients and Methods: 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Results: Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. Conclusions: The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.
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Affiliation(s)
- Semiha Bahceci Erdem
- Department of Pediatric Allergy, Dr. Behcet Uz Children's Hospital, Izmir, Turkey
| | - Hikmet Tekin Nacaroglu
- Department of Pediatric Allergy, Dr. Behcet Uz Children's Hospital, Izmir, Turkey
- Corresponding author: Hikmet Tekin Nacaroglu, Department of Pediatric Allergy, Dr. Behcet Uz Children's Hospital, Izmir, Turkey. Tel: +90-2324892315, Fax: +90-2324116319, E-mail:
| | | | - Ilker Gunay
- Department of Pediatric Allergy, Dr. Behcet Uz Children's Hospital, Izmir, Turkey
| | - Demet Can
- Department of Pediatric Allergy, Dr. Behcet Uz Children's Hospital, Izmir, Turkey
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Xu Y, Zhang J, Wang J. The efficacy and safety of selective H1-antihistamine versus leukotriene receptor antagonist for seasonal allergic rhinitis: a meta-analysis. PLoS One 2014; 9:e112815. [PMID: 25383622 PMCID: PMC4226613 DOI: 10.1371/journal.pone.0112815] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Accepted: 10/15/2014] [Indexed: 12/12/2022] Open
Abstract
Background Both selective H1-antihistamine (SAH) and leukotriene receptor antagonist (LTRA) have been shown to be effective in treating patients with seasonal allergic rhinitis (SAR), but it is still uncertain which treatment option is optimal. This meta-analysis was aimed to compare the efficacy and safety of SAH and LTRA for SAR. Materials and Methods PubMed, EMBASE and the Cochrane Library were searched for all eligible studies that compared the efficacy and safety of SAH and LTRA for SAR up to September 7, 2014. The pooled mean difference (MD), odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a fixed- or random-effects model. Results Nine studies with 5781 SAR patients were included. The results showed that SAH is superior to LTRA in terms of the daytime eye symptoms score (DESS) and composite symptoms score (CSS) for SAR (MD = 0.06, 95% CI, 0.03 to 0.10, P = 0.000, I2 = 99%; MD = 0.03, 95% CI, 0.01 to 0.05, P = 0.010, I2 = 98%), whereas LTRA overmatched SAH with respect to the night-time symptoms score (NSS) (MD = −0.04, 95% CI, −0.05 to −0.02, P = 0.000, I2 = 97%). Additionally, the results of subgroup analysis indicated that the dose, duration and gender of the patients might impact the comparisons of the effects of SAH and LTRA on their efficacy for SAR. Conclusion This meta-analysis suggested that SAH and LTRA have similar effects and safety for SAR, but SAH is more appropriate for daytime nasal symptoms (congestion, rhinorrhea, pruritus and sneezing), while LTRA is better suited for nighttime symptoms (difficulty going to sleep, nighttime awakenings, and nasal congestion on awakening), respectively. Meanwhile, the dose, duration and gender of patients may influence the anti-SAR effects of SAH and LTRA.
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Affiliation(s)
- Yu Xu
- Department of Otolaryngology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
- * E-mail:
| | - Jixiang Zhang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
| | - Jun Wang
- Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
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Licari A, Ciprandi G, Marseglia A, Castagnoli R, Barberi S, Caimmi S, Marseglia GL. Current recommendations and emerging options for the treatment of allergic rhinitis. Expert Rev Clin Immunol 2014; 10:1337-1347. [PMID: 25225773 DOI: 10.1586/1744666x.2014.955476] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Allergic rhinitis (AR) is one of the most common diseases and represents a global health problem, currently affecting up to 30% of the general population, with a continuously increasing prevalence and significant comorbidities and complications. The aim of this review is to provide an update on AR treatment, with a focus on current therapies defined by AR and its impact on asthma guidelines and with a particular emphasis on new and future therapeutic perspectives.
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Affiliation(s)
- Amelia Licari
- Department of Pediatrics, Immuno-Pneumo-Allergy Unit, University of Pavia, Fondazione IRCCS San Matteo, Pavia, Italy
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Devillier P, Dreyfus JF, Demoly P, Calderón MA. A meta-analysis of sublingual allergen immunotherapy and pharmacotherapy in pollen-induced seasonal allergic rhinoconjunctivitis. BMC Med 2014; 12:71. [PMID: 24885894 PMCID: PMC4101870 DOI: 10.1186/1741-7015-12-71] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Accepted: 03/31/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible. METHODS We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo. RESULTS Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast. CONCLUSIONS In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.
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Affiliation(s)
- Philippe Devillier
- UPRES EA 220 & Clinical Research Department, Foch Hospital, University of Versailles Saint-Quentin, Suresnes, France
- Biostatistics Unit, Clinical Research Department, Foch Hospital, Suresnes, France
| | | | - Pascal Demoly
- EPAR INSERM U707, Allergy Division, Pulmonology Department, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France, and Institut Pierre Louis d’Epidémiologie et de Santé Publique, Faculté de Médecine, Université Pierre et Marie Curie, Paris, France
| | - Moisés A Calderón
- Section of Allergy and Clinical Immunology, Imperial College London-NHLI, Royal Brompton Hospital, Dovehouse Street, London, UK
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Aung YN, Majaesic C, Senthilselvan A, Mandhane PJ. Physician specialty influences important aspects of pediatric asthma management. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2014; 2:306-12.e5. [PMID: 24811022 DOI: 10.1016/j.jaip.2013.12.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Revised: 11/25/2013] [Accepted: 12/16/2013] [Indexed: 10/25/2022]
Abstract
BACKGROUND Physician training influences patient care. OBJECTIVE To compare asthma management and change in the percentage predicted FEV1 among pediatric physician specialties. METHODS A retrospective cohort of children 6 years of age or older, seen in a multidisciplinary asthma clinic between 2009 and 2010, and followed to 2012, was completed to examine differences in asthma outcomes by specialty (2 pediatricians, 3 pediatric allergists, 5 pediatric respirologists). Univariate analyses compared investigation, including allergy testing (skin prick or RAST), comorbid conditions, and prescription by specialty. Multivariate regression, which controlled for random effect of the individual physician, examined specialty differences for prescribed inhaled corticosteroids (ICS) and changes in percentage predicted FEV1. RESULTS More than 56% of the patients (309/548) were seen by pediatric respirologists, 26% by pediatric allergists, and 18% by pediatricians. Physician specialty influences investigation requested, comorbid diagnoses, treatment, and improvement in FEV1. Pediatric allergists' patients had more allergy tests, were more likely to be diagnosed with allergic rhinitis and, consequently, were more likely to be prescribed nasal steroids than pediatricians and pediatric respirologists. Pediatricians were less likely to prescribe ICS (odds ratio 0.39 [95% CI, 0.15-0.96]; P < .05) than pediatric allergists, with the greatest difference in ICS prescription among children with a percentage predicted FEV1 ≥ 80%. Improvement in FEV1 among children who received care with pediatric allergists was higher than those seen by pediatricians (13%; P < .001) and pediatric respirologists (8%; P = .005). CONCLUSIONS Patient management domains with the greatest room for discretion (investigations, comorbid diagnoses, and treatment with ICS among children with normal lung function) are most heavily influenced by physician specialty. These results have implications for asthma management at the patient level and in future practice guidelines.
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Affiliation(s)
- Yin Nwe Aung
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; School of Public Health, University of Alberta, Edmonton, Alberta, Canada
| | - Carina Majaesic
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada
| | | | - Piushkumar J Mandhane
- Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada; School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
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Clicked cinnamic/caffeic esters and amides as radical scavengers and 5-lipoxygenase inhibitors. INTERNATIONAL JOURNAL OF MEDICINAL CHEMISTRY 2014; 2014:931756. [PMID: 25383225 PMCID: PMC4207410 DOI: 10.1155/2014/931756] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Revised: 12/12/2013] [Accepted: 12/13/2013] [Indexed: 01/17/2023]
Abstract
5-Lipoxygenase (5-LO) is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a-h and amides 9a-h as well as caffeic esters 15a-h and amides 16a-h were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes. All caffeic analogs are proved to be good radical scavengers (IC50: 10-20 μM). Esters 15g and 15f possessed excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized esters possess activities rivaling Zileuton in stimulated human polymorphonuclear leukocytes.
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Hosoya K, Masuno S, Hashiguchi K, Okubo K. Placebo-controlled study with OHIO chamber of prophylactic pranlukast for children with Japanese cedar pollinosis: TOPIC-J III study. J Drug Assess 2014; 3:51-9. [PMID: 27536454 PMCID: PMC4937631 DOI: 10.3109/21556660.2014.960969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2014] [Indexed: 12/02/2022] Open
Abstract
Objective This double-blind, placebo-controlled comparative study was designed to investigate whether pranlukast dry syrup, a leukotriene receptor antagonist, has a protective effect against priming, controlled pollen exposure, and natural pollen exposure in children with Japanese cedar pollinosis. Research design and methods Thirty children aged 12–15 years with Japanese cedar pollinosis (positive skin test for Japanese cedar pollen), who had suffered from pollinosis for at least 2 years and developed severe nasal obstruction when exposed to Japanese cedar pollen, were enrolled in this study. They were randomly allocated to treatment with pranlukast or placebo orally after breakfast and dinner for 8 weeks during the Japanese cedar pollen season. Soon after the start of the pollen season, all subjects underwent a challenge by exposure for 3 h to Japanese cedar pollen (8000 grains/m3) in an artificial exposure chamber (OHIO chamber). Clinical trial registration The University Hospital Medical Information Network in Japan (UMIN000009840). Main outcome measures The effect of pranlukast was evaluated using self-rating of nasal symptoms by the subjects and measurement of eosinophil cationic protein in nasal discharge specimens. Results Scores for the symptoms of pollinosis were lower in the pranlukast group than in the placebo group during treatment in the priming state, as well as after controlled pollen exposure and natural pollen exposure. Pranlukast significantly improved the score for nasal obstruction, compared with placebo. A correlation was found between changes of the scores for symptoms of pollinosis and changes of the eosinophil cationic protein level. Conclusions These results confirm a protective effect of pranlukast against both priming and challenge (controlled and natural) with Japanese cedar pollen. The present findings suggested that pranlukast dry syrup may be useful for prophylaxis against pollinosis in children.
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Affiliation(s)
- Kei Hosoya
- Department of Otorhinolaryngology, Nippon Medical School, TokyoJapan
| | - Satoru Masuno
- Department of Otorhinolaryngology, Nippon Medical School, TokyoJapan
| | | | - Kimihiro Okubo
- Department of Otorhinolaryngology, Nippon Medical School, TokyoJapan
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Yilmaz O, Altintas D, Rondon C, Cingi C, Oghan F. Effectiveness of montelukast in pediatric patients with allergic rhinitis. Int J Pediatr Otorhinolaryngol 2013; 77:1922-4. [PMID: 24210867 DOI: 10.1016/j.ijporl.2013.10.006] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2013] [Revised: 10/05/2013] [Accepted: 10/09/2013] [Indexed: 11/24/2022]
Abstract
Allergic rhinitis (AR) is one of the most common chronic diseases of childhood and carries significant morbidity as well as physical and psychosocial consequences. Therapy aims to alleviate clinical symptoms, prevent complications and improve psychosocial consequences. Leukotrienes which are amongst the main mediators in pathogenesis of AR have chemotactic properties and lead to increased vascular permeability. Thus, leukotriene antagonism may be an effective therapeutic option in treatment of allergic diseases, specifically AR. Montelukast which is a leukotriene receptor type I inhibitor has variable efficacy in children with AR and the guidelines recommend its use in children with seasonal AR aged six years and above. Although its efficacy is inferior to anti-histamines and intranasal corticosteroids, combination treatment may warrant clinical efficacy. Therefore, montelukast may be considered to be a well-tolerated therapeutic option for children with AR with minor side effects though long term results need to be assessed. In conclusion, larger scale research enrolling pediatric cases with seasonal and persistent AR are required before concise recommendations about montelukast use in pediatric AR can be made.
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Affiliation(s)
- Ozge Yilmaz
- Celal Bayar University Medical Faculty, Department of Pediatric Allergy and Pulmonology, Manisa, Turkey.
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Scott JP, Peters-Golden M. Antileukotriene agents for the treatment of lung disease. Am J Respir Crit Care Med 2013; 188:538-44. [PMID: 23822826 DOI: 10.1164/rccm.201301-0023pp] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Leukotrienes (LTs) C4, D4, and E4, collectively termed cysteinyl LTs (cysLTs), are lipid mediators formed by the 5-lipoxygenase (5-LO) pathway of arachidonic acid metabolism. Originally recognized for their potent bronchoconstrictor actions, they were subsequently determined also to promote inflammation, microvascular permeability, and mucus secretion. These actions that are so central to asthma pathophysiology are mediated to a significant extent by ligation of the cysLT receptor 1 (CysLT1). Antagonism of CysLT1 and inhibition of 5-LO have both been shown to have clinical use in the management of asthma, but substantial interindividual heterogeneity is observed in the response to these agents. In this article, we review the biologic actions of LTs, their biosynthetic pathways and cognate receptors, the pharmacology of available anti-LT agents, and the clinical evidence for the use of anti-LT agents as monotherapy and combination therapy in asthma. We also consider heterogeneity of response, the possible roles of cysLT receptors other than CysLT1, the role of another class of LT, LTB4, and the potential role of LTs in lung diseases other than asthma.
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Affiliation(s)
- Jacob P Scott
- Division of Pulmonary and Critical Care Medicine, University of Michigan Health System, Ann Arbor, USA
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Arm JP, Boyce JA, Wang L, Chhay H, Zahid M, Patil V, Govindarajulu U, Ivester P, Weaver KL, Sergeant S, Israel E, Chilton FH. Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene generation in mild asthmatics. Lipids Health Dis 2013; 12:141. [PMID: 24088297 PMCID: PMC3851449 DOI: 10.1186/1476-511x-12-141] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2013] [Accepted: 09/26/2013] [Indexed: 01/07/2023] Open
Abstract
Background Dietary supplementation with botanical oils that contain n-6 and n-3 eighteen carbon chain (18C)-PUFA such as γ linolenic acid (GLA, 18:3n-6), stearidonic acid (SDA, 18:4n-3) and α linolenic acid (ALA, 18:3n-3) have been shown to impact PUFA metabolism, alter inflammatory processes including arachidonic acid (AA) metabolism and improve inflammatory disorders. Methods The diet of mild asthmatics patients was supplemented for three weeks with varying doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week wash out period followed. The impact of these dietary manipulations was evaluated for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo leukotriene generation from stimulated leukocytes. Results Supplementation with several EO/BO combinations increased circulating 20–22 carbon (20–22C) PUFAs, including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo-gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and inflammation without impacting circulating AA levels. BO/EO combinations also inhibited ex vivo leukotriene generation with some combinations attenuating cysteinyl leukotriene generation in stimulated basophils by >50% and in stimulated neutrophils by >35%. Conclusions This study shows that dietary supplementation with BO/EO alters 20–22C PUFA levels and attenuates leukotriene production in a manner consistent with a reduction in inflammation.
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Affiliation(s)
- Jonathan P Arm
- Department of Physiology/Pharmacology, Wake Forest School of Medicine, Medical Center Blvd, 27157, Winston-Salem, NC, USA.
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Cingi C, Oghan F, Eskiizmir G, Yaz A, Ural A, Erdogmus N. Desloratadine-montelukast combination improves quality of life and decreases nasal obstruction in patients with perennial allergic rhinitis. Int Forum Allergy Rhinol 2013; 3:801-6. [DOI: 10.1002/alr.21185] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Revised: 04/08/2013] [Accepted: 04/23/2013] [Indexed: 11/11/2022]
Affiliation(s)
- Cemal Cingi
- Department of Otorhinolaryngology, Faculty of Medicine; Osmangazi University; Eskisehir Turkey
| | - Fatih Oghan
- Department of Otorhinolaryngology, Faculty of Medicine; Dumlupinar University; Kutahya Turkey
| | - Gorkem Eskiizmir
- Department of Otorhinolaryngology, Faculty of Medicine; Celal Bayar University; Manisa Turkey
| | - Aytekin Yaz
- Department of Otorhinolaryngology; Tepecik Training and Research Hospital; Izmir Turkey
| | - Ahmet Ural
- Department of Otorhinolaryngology, Faculty of Medicine; Karadeniz Technical University; Trabzon Turkey
| | - Nagehan Erdogmus
- Department of Otorhinolaryngology, Faculty of Medicine; Osmangazi University; Eskisehir Turkey
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Kuroda W, Kitamura Y, Mizuguchi H, Miyamoto Y, Kalubi B, Fukui H, Takeda N. Combination of leukotoriene receptor antagonist with antihistamine has an additive suppressive effect on the up-regulation of H1-receptor mRNA in the nasal mucosa of toluene 2,4-diisocyanate-sensitized rat. J Pharmacol Sci 2013; 122:55-8. [PMID: 23615224 DOI: 10.1254/jphs.12250sc] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022] Open
Abstract
An attempt was made to clarify the additive suppressive effects of pranlukast, a cysteinyl leukotriene-receptor (LTR) antagonist, in combination with chlorpheniramine, an antihistamine, on the up-regulation of histamine H1-receptor (H1R) mRNA in toluene 2,4-diisocyanate (TDI)-sensitized rats. Although pre-treatment with pranlukast partially, but significantly, suppressed TDI-induced up-regulation of H1R mRNA and nasal symptoms, pre-treatment with the combination of pranlukast and chlorpheniramine significantly suppressed them in a manner greater than either drug alone. These findings suggest that the additive therapeutic effect of the combination of LTR antagonist and antihistamine is due to their additive suppression of H1R up-regulation.
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Affiliation(s)
- Wakana Kuroda
- Department of Otolaryngology, Institute of Health Biosciences, The University of Tokushima Graduate School, Japan
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Gane J, Buckley R. Leukotriene receptor antagonists in allergic eye disease: a systematic review and meta-analysis. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2012; 1:65-74. [PMID: 24229824 DOI: 10.1016/j.jaip.2012.07.001] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/03/2012] [Accepted: 07/06/2012] [Indexed: 01/13/2023]
Abstract
BACKGROUND Allergic eye diseases are common and cause significant morbidity. Leukotrienes are implicated in the pathogenesis of seasonal and perennial allergic conjunctivitis (AC), commonly seen in conjunction with allergic rhinitis, and in vernal keratoconjunctivitis and atopic keratoconjunctivitis. OBJECTIVES To assess the available evidence for an effect of leukotriene receptor antagonists (LTRAs) on the ocular symptoms of allergic eye diseases. METHODS Selected studies, identified with systematic review search methods, were single/double-blind, randomized, controlled trials that compared LTRAs with other common treatments. RESULTS Eighteen trials, using the LTRA montelukast (in AC only), were identified. Six studies were suitable for meta-analysis, in patients with seasonal AC [treated over a 2-week period, symptoms scored 0 (mild) to 3 (severe)]. These trials were at low risk of bias without significant heterogeneity. Six trials were analyzed and showed that montelukast improved patients' ocular symptoms to a greater extent than placebo, with a difference in mean change-from-baseline score of -0.10 (95% CI, -0.14 to -0.07; P < .00001). Three trials compared montelukast with oral antihistamine. The difference in mean change-from-baseline score was 0.08 (95% CI, 0.02 to 0.14; P = .007), in favor of antihistamines. Two trials compared montelukast and oral antihistamine with placebo. The difference in mean change-from-baseline score was -0.30 (95% CI, -0.38 to -0.21; P < .00001), in favor of combination treatment. CONCLUSIONS In seasonal AC LTRAs are more efficacious than placebo but less efficacious than oral antihistamines in adult patients. Clinical trials should be conducted to determine whether combination treatment with LTRA and oral antihistamine has a synergistic effect. Further research is required to clarify the role of LTRAs in other allergic eye diseases.
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Affiliation(s)
- Jennie Gane
- Clinical Research Fellow, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham B15 2WB, United Kingdom.
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Hashiguchi K, Okubo K, Wakabayashi KI, Tanaka N, Watada Y, Suematsu K, Gotoh M. The assessment of the optimal duration of early intervention with montelukast in the treatment of Japanese cedar pollinosis symptoms induced in an artificial exposure chamber. J Drug Assess 2012; 1:40-7. [PMID: 27536427 PMCID: PMC4980728 DOI: 10.3109/21556660.2012.728547] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/06/2012] [Indexed: 11/25/2022] Open
Abstract
Objective The study objective was to investigate the prophylactic efficacy of montelukast (MLK) 10 mg in suppressing seasonal allergic rhinitis (SAR) symptoms induced by Japanese cedar (JC) pollen and to determine how many days before exposure to JC in the artificial exposure chamber (OHIO chamber) would be optimal to start administration. Methods This was a single-institution, double-blind, randomized placebo-controlled four-group parallel inter-group comparison study. Adult volunteers with JC pollinosis were divided into four groups: an MLK 7-day administration group (n = 27), an MLK 3-day administration group (n = 27), an MLK 1-day administration group (n = 26), and a placebo group (n = 26). The mean change in total nasal symptom scores (nasal obstruction, nasal discharge and sneezing) (TNSS) and each of the nasal symptom scores during exposure of JC pollen in the OHIO chamber were investigated. Results The mean change in TNSS was significantly lower in the MLK treatment group, regardless of the number of days of administration, than in the placebo group (p = 0.0192). The results for the individual nasal symptoms showed that nasal obstruction was significantly suppressed in the 1-day administration group as compared with placebo (p = 0.0076), but no differences were found in sneezing score between any of the groups. For nasal discharge, we found a trend towards the effect clearing up after 3 days of administration. No serious adverse events were observed during the study. Conclusion Although this study was acute and this artificial exposure model was conducted out of the pollen season, nasal symptoms that developed in the pollen exposure chamber, especially nasal obstruction, were significantly suppressed by starting oral administration of MLK 10 mg at least 1 day before exposure. These results suggest that prophylactic administration of MLK is effective and safe in the treatment of SAR.
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Affiliation(s)
| | - Kimihiro Okubo
- Department of Otolaryngology, Nippon Medical School, TokyoJapan
| | | | - Nobuaki Tanaka
- Tanaka ENT Clinic, Tokyo, Japan; Department of Otorhinolaryngology, Tokyo Women's Medical University Medical Center East, TokyoJapan
| | - Yukiko Watada
- Department of Otorhinolaryngology, Keio University School of Medicine, TokyoJapan
| | - Kiyochika Suematsu
- Pharmaceutical Department, Medical Corporation Shinanokai, Samoncho Clinic, TokyoJapan
| | - Minoru Gotoh
- Department of Otolaryngology, Nippon Medical School, TokyoJapan
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Gotoh M, Suzuki H, Okubo K. Delay of onset of symptoms of Japanese cedar pollinosis by treatment with a leukotriene receptor antagonist. Allergol Int 2011; 60:483-9. [PMID: 21778814 DOI: 10.2332/allergolint.10-oa-0285] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2010] [Accepted: 02/25/2011] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Leukotriene receptor antagonists (LTRAs) are effective for prophylactic treatment of pollinosis based on studies showing that administration of LTRAs prior to or at the start of the pollen season reduces symptoms and QOL disturbance at the peak of pollen dispersal. Two goals of prophylactic treatment of pollinosis are use of fewer types of drugs and delay of onset of symptoms and impairement of QOL. Therefore, this study was performed to determine if pranlukast, a LTRA, met these goals in treatment of pollinosis. METHODS Pranlukast or placebo was administered to patients who visited our hospital immediately before the start of Japanese cedar pollen dispersal. The study was performed for 4 weeks as a double blind randomized trial. Subsequently, all patients were given pranlukast for a further 4 weeks from the peak until the end of pollen dispersal. The incidence of symptoms and use of concomitant drugs were investigated from daily nasal allergy records kept by patients. QOL was evaluated using the JRQLQ questionnaire. RESULTS In the double blind period of the study, the percentage of patients who used concomitant drugs for nasal symptoms was significantly lower in the pranlukast group compared to the placebo group. Development of nasal symptoms (sneezing, runny nose and nasal congestion) and disturbance of daily activities were significantly delayed in the pranlukast group. No serious adverse reactions occurred in the pranlukast group and no patient withdrew from treatment with pranlukast. CONCLUSIONS Pranlukast is effective for prophylactic treatment of pollinosis.
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Affiliation(s)
- Minoru Gotoh
- Department of Otorhinolaryngology, Nippon Medical School, Tokyo, Japan.
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Subcutaneous immunotherapy and pharmacotherapy in seasonal allergic rhinitis: A comparison based on meta-analyses. J Allergy Clin Immunol 2011; 128:791-799.e6. [DOI: 10.1016/j.jaci.2011.03.049] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2010] [Revised: 03/22/2011] [Accepted: 03/31/2011] [Indexed: 11/19/2022]
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Lin L, Zheng C, Zhang L, Da C, Zhao K. 2-Aminoethoxydiphenyl borate administration into the nostril alleviates murine allergic rhinitis. Am J Otolaryngol 2011; 32:318-328. [PMID: 20832906 DOI: 10.1016/j.amjoto.2010.07.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2009] [Revised: 05/18/2010] [Accepted: 07/17/2010] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Orai1 is the pore-forming subunit of the Ca(2+) release-activated Ca(2+) channels and plays a key role in the store-operated Ca(2+) entry. However, little is known about the function of this pathway in allergic rhinitis (AR). In this study, we examined whether the intervention of Orai1 pathway was capable of controlling IgE-mediated allergic reactions by using AR mice models. MATERIALS AND METHODS We used Western blotting and real-time reverse transcription polymerase chain reaction to evaluate Orai1 expression in nasal mucosa and nasal-associated lymphoid tissue (NALT) of normal, control, and 2-aminoethoxydiphenyl borate (2-APB)-treated mice. In addition, we analyzed concentrations of nasal lavage fluid leukotriene C4 (LTC4), eosinophil cation protein (ECP), ovalbumin-specific IgE, and interleukin-4 (IL-4) through enzyme-linked immunosorbent assay and measured messenger RNA (mRNA) levels of LTC4 synthase and ECP in nasal mucosa, and germline Cɛ transcription and IL-4 mRNA in NALT by using real-time reverse transcription polymerase chain reaction among groups. RESULTS 2-Aminoethoxydiphenyl borate administration into the nostril reduced numbers of sneezing and nasal rubbing as well as counts of invasive eosinophils in treated mice compared with those in control ones. Furthermore, the administration suppressed Orai1 expression in nasal mucosa and NALT of treated mice compared with that of control ones. Similarly, 2-APB treatment restrained nasal lavage fluid LTC4, ECP, ovalbumin-specific IgE, and IL-4 and their corresponding mRNAs in the previously mentioned tissues of treated mice in comparison with those of control ones. CONCLUSION Our results indicate that 2-APB treatment effectively alleviates murine AR through pleiotropic activities.
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MESH Headings
- Administration, Intranasal
- Animals
- Blotting, Western
- Boron Compounds/administration & dosage
- Calcium Channels/biosynthesis
- Calcium Channels/genetics
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Female
- Gene Expression Regulation
- Glutathione Transferase/biosynthesis
- Glutathione Transferase/genetics
- Mice
- Mice, Inbred BALB C
- Nasal Mucosa/metabolism
- ORAI1 Protein
- RNA, Messenger/genetics
- Real-Time Polymerase Chain Reaction
- Rhinitis, Allergic, Perennial/drug therapy
- Rhinitis, Allergic, Perennial/genetics
- Rhinitis, Allergic, Perennial/metabolism
- Treatment Outcome
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Affiliation(s)
- Lin Lin
- Department of Otorhinolaryngology-Head and Neck Surgery, Huashan Hospital of Fudan University, Shanghai, China
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Kajiwara D, Aoyagi H, Shigeno K, Togawa M, Tanaka K, Inagaki N, Miyoshi K. Role of hematopoietic prostaglandin D synthase in biphasic nasal obstruction in guinea pig model of experimental allergic rhinitis. Eur J Pharmacol 2011; 667:389-95. [PMID: 21645503 DOI: 10.1016/j.ejphar.2011.05.041] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2010] [Revised: 05/19/2011] [Accepted: 05/22/2011] [Indexed: 11/24/2022]
Abstract
We investigated the role of hematopoietic prostaglandin D synthase (H-PGDS) in biphasic nasal obstruction in allergic rhinitis using a new specific inhibitor, (N-methoxy-N-methyl)-4-(5-benzoylbenzimidazole-2-yl)-3,5-dimethylpyrrole-2-carboxamide hydrochloride (TAS-204). First, we developed a novel guinea pig model of allergic rhinitis. Guinea pigs sensitized to ovalbumin without adjuvant were challenged with intranasal exposure to ovalbumin once a week. After the 3rd antigen challenge, they exhibited biphasic nasal obstruction. Additionally, analysis of nasal lavage fluid revealed an increase in the level of prostaglandin D(2) in both early and late phases. Treatment with oral TAS-204 for 15 days during the period of antigen challenges suppressed increases in nasal airway resistance in both phases. It is noteworthy that the late phase nasal obstruction was almost completely abrogated by inhibiting H-PGDS alone. Eosinophil infiltration in nasal lavage fluid and nasal hyperresponsiveness to histamine was also reduced by TAS-204 administration. These findings suggest that H-PGDS plays a critical role in the development of allergic rhinitis, especially in the induction of late phase nasal obstruction.
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Affiliation(s)
- Daisuke Kajiwara
- Discovery & Development Laboratory 2, Taiho Pharmaceutical Co. Ltd., 3, Ohkubo, Tsukuba, Ibaraki 300-2611, Japan.
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Abstract
Allergic rhinitis affects millions of Americans and the numbers continue to increase. Fortunately, there exists a wide array of pharmacotherapeutic options with relatively safe side effect profiles for the management of the varying subtypes. Additionally, there are newer agents on the horizon. The efficacies of intranasal corticosteroids, antihistamines, combination topical therapy, leukotriene inhibitors, mast cell stabilizers, anticholinergics, mucolytics, decongestants, and anti-IgE are reviewed.
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Cingi C, Gunhan K, Gage-White L, Unlu H. Efficacy of leukotriene antagonists as concomitant therapy in allergic rhinitis. Laryngoscope 2010; 120:1718-23. [DOI: 10.1002/lary.20941] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Boulay ME, Duchesneau E, Jacques E, Chakir J, Boulet LP. CysLT1-R expression following allergen provocation in asthma and allergic rhinitis. Prostaglandins Leukot Essent Fatty Acids 2010; 83:15-22. [PMID: 20462748 DOI: 10.1016/j.plefa.2010.02.033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2009] [Revised: 01/25/2010] [Accepted: 02/22/2010] [Indexed: 11/22/2022]
Abstract
Cysteinyl leukotrienes (CysLTs) contribute to allergic and inflammatory diseases through CysLT(1)-R. We aimed to assess CysLT(1)-R mRNA expression in induced sputum of rhinitics with or without asthma before and following allergen challenges. Both groups underwent nasal and "low dose" lung allergen challenges. Asthmatics also underwent "standard" lung challenge. Sputum was obtained before and at different time-points following the challenges for CysLT(1)-R, 5-lipoxygenase (5-LO), and eotaxin mRNA assessments. At baseline, there was no difference in mediator levels between groups. An increase in CysLT(1)-R mRNA (p=0.04) and a trend towards an increase in 5-LO and eotaxin (p=0.06 for both) at 24 h post-nasal challenge were observed. Following "low dose" lung allergen challenge, there was a trend towards an increase in CysLT(1)-R (p=0.07). In conclusion, CysLT(1)-R gene expression changes can be detected in sputum following allergen challenges. No difference was observed between groups, suggesting that changes in CysLT(1)-R expression occur whether or not the subject has concurrent asthma.
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Affiliation(s)
- Marie-Eve Boulay
- Unité de recherche en pneumologie, Centre de recherche, de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC G1V 4G5, Canada
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Esteitie R, deTineo M, Naclerio RM, Baroody FM. Effect of the addition of montelukast to fluticasone propionate for the treatment of perennial allergic rhinitis. Ann Allergy Asthma Immunol 2010; 105:155-61. [PMID: 20674827 DOI: 10.1016/j.anai.2010.05.017] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2010] [Revised: 05/18/2010] [Accepted: 05/18/2010] [Indexed: 11/24/2022]
Abstract
BACKGROUND Guidelines for the treatment of patients with allergic rhinitis (AR) recommend intranasal corticosteroids as first-line therapy. In clinical trials, however, only 50% of patients obtain excellent symptom control. OBJECTIVE To evaluate the effectiveness of montelukast add-on therapy in patients with perennial AR (PAR) who have incomplete relief of symptoms after 2 weeks of treatment with intranasal fluticasone propionate. METHODS We performed a 4-week parallel, randomized, double-blind, placebo-controlled trial. One hundred two patients with a history of PAR and a positive skin test reaction to perennial allergens were recruited. They completed the Rhinitis Quality of Life Questionnaire (RQLQ) and were given intranasal fluticasone propionate, 200 microg daily. They were asked to complete symptom diary cards twice daily. After 2 weeks of treatment, patients with a mean total nasal symptom score of at least 4 during the past week (n = 54) were randomized to receive either montelukast (n = 28) or placebo (n = 26) in addition to the continued use of fluticasone propionate. At weeks 3 and 4, the RQLQ was completed again and symptom diary cards were collected. RESULTS Compared with baseline, there were significant improvements in almost all domains of the RQLQ while taking fluticasone propionate (P < .001). A similar trend was observed for nasal symptom scores. After randomization to receive montelukast or placebo, there were no significant differences in RQLQ measures or nasal symptom scores between the groups during the 2 weeks of combination therapy. CONCLUSION The addition of montelukast to an intranasal corticosteroid for the treatment of PAR with residual symptoms is no more effective than is placebo.
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Affiliation(s)
- Rania Esteitie
- Section of Otolaryngology-Head and Neck Surgery, The University of Chicago Medical Center and Pritzker School of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
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Abstract
The increasing burden of asthma in both primary and secondary care has led to extensive research into its genetics, pathophysiology and treatment over the past few decades. Inhaled corticosteroids remain an integral component in all but the mildest disease, although despite a low-to-moderate dose, many individuals remain symptomatic. In patients with persistent symptoms despite inhaled corticosteroids, a variety of different nonsteroidal second-line therapies are available as add-on therapy. In this review, existing and potential future pharmacological strategies involved in the management of asthma will be highlighted.
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Affiliation(s)
- Graeme P Currie
- Aberdeen Royal Infirmary, Department of Respiratory Medicine, Foresterhill, Aberdeen AB25 2ZN, UK.
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Bjermer L. Montelukast in the treatment of asthma as a systemic disease. Expert Rev Clin Immunol 2010; 1:325-36. [PMID: 20476984 DOI: 10.1586/1744666x.1.3.325] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Asthma affects 300 million people worldwide. The common association of asthma with allergic rhinitis and the presence of proinflammatory mediators in the circulation of patients provide strong evidence for the need to treat asthma as a systemic disease. The leukotriene receptor antagonist montelukast is a disease-specific oral medication that has dual effects on airway smooth muscle cells and inflammatory processes. This review describes recent randomized, controlled studies of montelukast in asthma and allergic rhinitis in adults and children as young as 3 months old. Montelukast treatment consistently produced significant reductions in asthma exacerbations. While many patients may benefit from montelukast as monotheray, combination treatment for chronic asthma with inhaled corticosteroids is advocated as being rational. Significant improvements in symptoms and quality of life were observed in allergic rhinitis patients. Montelukast is well tolerated in patients of all ages. Long-term studies are underway to determine its effects on airway remodeling.
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Affiliation(s)
- Leif Bjermer
- Department of Respiratory Medicine and Allergology, University Hospital, SE 221 85 Lund, Sweden.
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Effects of montelukast on quality of life in patients with persistent allergic rhinitis. Otolaryngol Head Neck Surg 2010; 142:654-8. [PMID: 20416451 DOI: 10.1016/j.otohns.2010.01.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2009] [Revised: 12/30/2009] [Accepted: 01/12/2010] [Indexed: 11/23/2022]
Abstract
OBJECTIVE To determine the effects of montelukast monotherapy on health-related quality of life (HRQL) in patients with persistent allergic rhinitis. STUDY DESIGN The study was placebo-controlled, randomized, and double blinded. SETTING Tertiary university hospital. SUBJECTS AND METHODS There were 46 patients in the study group and 24 patients in the control group, all of whom had a diagnosis of persistent allergic rhinitis of at least two years. The patients were evaluated at two control visits after the diagnosis. The study group was given 10-mg montelukast oral tablets, while the control group was given a placebo, and these were taken daily for one month. For evaluation of HRQL in both groups, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was used. RESULTS There was a larger decrease in the overall RQLQ score for the group using montelukast compared with the placebo group (P < 0.001). The difference between scores at baseline versus the end of the first month for all domains was statically significant in both the placebo group and study group (P < 0.001). The difference in change from baseline to the end of the first month (treatment difference) between the placebo group and the study group was statically significant, in favor of the study group, for sleep, practical problems, nasal problems, and activities that have been limited by nose or eye symptoms, and for overall score (P < 0.001, P < 0.001, P = 0.003, P < 0.001, and P < 0.001, respectively). CONCLUSION Montelukast is a drug that improves the disease-specific quality of life in patients being treated for persistent allergic rhinitis better than placebo.
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Meltzer EO, Caballero F, Fromer LM, Krouse JH, Scadding G. Treatment of congestion in upper respiratory diseases. Int J Gen Med 2010; 3:69-91. [PMID: 20463825 PMCID: PMC2866555 DOI: 10.2147/ijgm.s8184] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2010] [Indexed: 12/19/2022] Open
Abstract
Congestion, as a symptom of upper respiratory tract diseases including seasonal and perennial allergic rhinitis, acute and chronic rhinosinusitis, and nasal polyposis, is principally caused by mucosal inflammation. Though effective pharmacotherapy options exist, no agent is universally efficacious; therapeutic decisions must account for individual patient preferences. Oral H1-antihistamines, though effective for the common symptoms of allergic rhinitis, have modest decongestant action, as do leukotriene receptor antagonists. Intranasal antihistamines appear to improve congestion better than oral forms. Topical decongestants reduce congestion associated with allergic rhinitis, but local adverse effects make them unsuitable for long-term use. Oral decongestants show some efficacy against congestion in allergic rhinitis and the common cold, and can be combined with oral antihistamines. Intranasal corticosteroids have broad anti-inflammatory activities, are the most potent long-term pharmacologic treatment of congestion associated with allergic rhinitis, and show some congestion relief in rhinosinusitis and nasal polyposis. Immunotherapy and surgery may be used in some cases refractory to pharmacotherapy. Steps in congestion management include (1) diagnosis of the cause(s), (2) patient education and monitoring, (3) avoidance of environmental triggers where possible, (4) pharmacotherapy, and (5) immunotherapy (for patients with allergic rhinitis) or surgery for patients whose condition is otherwise uncontrolled.
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Affiliation(s)
- Eli O Meltzer
- Allergy and Asthma Medical Group and Research Center, San Diego, CA and Department of Pediatrics, University of California, San Diego, USA
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Quelles stratégies thérapeutiques dans la rhinite allergique ? REVUE FRANÇAISE D'ALLERGOLOGIE 2009. [DOI: 10.1016/s1877-0320(09)73415-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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