Prescribed Fenoterol and Death From Asthma in New Zealand, 1981-83; Case-Control Study

Crane, Julian; Flatt, A.; Jackson, Rod; Ball, Matthew; Pearce, Neil; Burgess, Carl; Kwong, Tai C.; Beasley, Richard

doi:10.1016/s0140-6736(89)92505-1

Cited by 539 publications

(199 citation statements)

References 17 publications

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“…Similar findings were reported for oral theophyllines 4,6,14). Some have shown an increased risk 14), some have not 4 6).…”

Section: Discussionsupporting

confidence: 68%

“…Many investigations were conducted to elucidate uncertainty about the confounding between severity and fenoterol use [4][5][6][7][8][9][10][11] Opinion is still divided: one is that fenoterol was not associated with severe life-threatening attacks (LTA) after controlling severity 8,10);and the other is that the association between fenoterol and asthma death was significant, but after adjustment for markers of asthma severity was made, there was no difference in the magnitude of the association between fenoterol and asthma death 4-7,9,11) In this paper, we report the results of a case-control study on prescribed drug therapy, severity, and the risk of death from asthma and LTA in Japan.…”

Section: Introductionmentioning

confidence: 99%

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A Case-control Study of Asthma Death and Life-threatening Attack: Their Possible Relationship with Prescribed Drug Therapy in Japan.

Tanihara

Nakamura

Matsui

et al. 2002

Journal of Epidemiology

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Sales of inhaled *2-agonist bronchodilators may be related to the increase in asthma deaths. The aim of this study is to find whether prescribed drug therapy was associated with the increased risk of death from asthma and life-threatening attacks (LTA). The "case" group comprised those under 35 years of age who expired or experienced LTA from January 1994 through December 1996. For each case, an age and sex matchedcontrol was selected from asthma patients. Hospital records were reviewed to obtain information on the prescribed drug therapy and clinical asthma severity for the cases and controls. Bivariate analysis with conditional logistic regression models for matched data sets were used to estimate theseverity-adjusted odds ratios for each asthma medication. Twenty-four fatal cases and 54 LTA cases were observed. The crude odds ratio of clinical severity (OR=9.33, 95%CI:2.84-30.7) was larger than unity and with statistical significance. After adjusting for clinical severity, the odds ratios computed for all *2-agonists delivered by metered dose inhaler (MDI) increased (OR=2.08, 95%CI:0.78-5.50) from that of crude analysis. Among those subjects under 20 years of age, the clinical severity-adjusted odds ratio for the use of all *2-agonists by MDI (OR=3.67, 95%CI:0.77-17.5) was higher than that of all subjects. The prescription of f32-agonists by MDI increased the risk of asthma death after taking clinical severity into account. Although not statistically significant, our results suggested that l32-agonists administered by a MDI might have increased the risk of asthma death and LTA in Japan because the magnitude of the effect was similar to that reported in other countries. J Epidemiol, 2002 ; 12:223-228 asthma, asthma death, life-threatening attack, f32-agonist, metered dose inhaler INTRODUCTIONIn the 1960s, asthma mortality was alluded to during an epidemic on the basis of an ecologic study in England and Wales 1,a and in Japan 3), suggesting that sales of inhaled B2-agonist bronchodilators may have been related to excessive asthma deaths during the epidemic. In the 1980s, a relation between inhaled fenoterol and increased risk of death from asthma was reported from New Zealand4-7). However, these findings might be due to a tendency to prescribe the drug more frequently for patients with severe asthma 8).Many investigations were conducted to elucidate uncertainty about the confounding between severity and fenoterol use 4-11) Opinion is still divided: one is that fenoterol was not associated with severe life-threatening attacks (LTA) after controlling severity 8,10);and the other is that the association between fenoterol and asthma death was significant, but after adjustment for markers of asthma severity was made, there was no difference in the magnitude of the association between fenoterol and asthma death 4-7,9,11) In this paper, we report the results of a case-control study on prescribed drug therapy, severity, and the risk of death from asthma and LTA in Japan. METHODS Case and Control SelectionIn Januar...

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“…Similar findings were reported for oral theophyllines 4,6,14). Some have shown an increased risk 14), some have not 4 6).…”

Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

A Case-control Study of Asthma Death and Life-threatening Attack: Their Possible Relationship with Prescribed Drug Therapy in Japan.

Tanihara

Nakamura

Matsui

et al. 2002

Journal of Epidemiology

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“…Fenoterol and clenbuterol are third-generation drugs with relatively long-lasting actions 33,34) and fenoterol has frequently been discussed in relation to asthma death. 35,36) As salbutamol exhibited less potent inhibitory effects on the mediator release than the other three agonists, higher concentrations were employed in the present experiments. These four agonists showed similar desensitizing effects on mediator release from cultured human mast cells in spite of their distinct characteristics, suggesting that the desensitizing phenomenon may not be affected significantly by the characteristics of each agonist under the present experimental conditions.…”

Section: -3)mentioning

confidence: 99%

Differential Effects of .BETA.2-Adrenoceptor Desensitization on the IgE-Dependent Release of Chemical Mediators from Cultured Human Mast Cells

Tsuji

Kato

Kimata

et al. 2004

Biological & Pharmaceutical Bulletin

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Agonist binding to b 2 -adrenoceptors causes activation of adenylate cyclase through coupling to a stimulatory component of GTP-binding protein (Gs protein) and results in an elevation of intracellular cAMP levels. cAMP plays an important role in inducing cellular responses as a second messenger. It is well known, however, that the responsiveness of b 2 -adrenoceptors wanes after continuous or repeated exposure to the agonists, a phenomenon referred to as desensitization.1-3) The initial step of the desensitization is caused by phosphorylation of intracellular domains of b 2 -adrenoceptors. The receptor phosphorylation results in an uncoupling between receptor proteins and Gs proteins. Two types of protein kinase are considered to be responsible for the phosphorylation. One is a cAMP-dependent protein kinase A (PKA) and the other is a cAMP-independent G proteincoupled receptor kinase such as b 2 -adrenergic receptor kinase (b-ARK). Phosphorylation by b-ARK facilitates the binding of b-arrestin to the receptors, which interferes with the receptor coupling to Gs protein. Prolonged exposure of the receptors to agonists may facilitate the receptor internalization, followed by their degradation. Furthermore, b 2 -adrenoceptor gene expression may be downregulated when cells are exposed continuously to the agonists for a long period. Although receptor desensitization is an important mechanism to maintain homeostasis, the same mechanism may interfere with the therapeutic effects of b 2 -adrenoceptor agonists. 4,5) It has been reported that b 2 -adrenoceptor agonists inhibit IgE-mediated release of mediators such as histamine, prostaglandin D 2 (PGD 2 ), and cysteinyl leukotrienes (LT) from human lung fragments, [6][7][8][9] and dispersed human lung and skin mast cells. [10][11][12][13] We also reported that b 2 -adrenoceptor agonists inhibit the chemical mediator release in cultured human mast cells.14-16) b 2 -Adrenoceptor agonists inhibit mediator release from human mast cells far more potently than disodium cromoglycate. 6,8,13,14) Furthermore, b 2 -adrenoceptor agonists inhibit PGD 2 and LT release more potently than histamine release from human mast cells. 11,13,14) On the other hand, desensitization has also been observed in the inhibition of human mast cell histamine release by b 2 -adrenoceptor agonists. [17][18][19] Chong and Peachell 18) reported that isoproterenol inhibition of histamine release from human lung mast cells is considerably more susceptible to desensitizing treatments than the isoproterenol relaxation of bronchial smooth muscle. In contrast to histamine release, however, desensitization of PGD 2 and LT release inhibition by b 2 -adrenoceptor agonists has rarely been investigated.In the present study therefore, we examined and compared the inhibitory effects of b 2 -adrenoceptor agonists on the release of histamine, PGD 2 , and LT from cultured human mast cells after prolonged treatment with the agonists. Laboratory and Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd.; Gunma 370-1295 ...

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“…Case-control studies performed in the following years have demonstrated that phenoterol use was associated with mortality independent of the severity of asthma. Mortality reduced as a result of warnings against using phenoterol at high dosages and the issue was suggested to be related with overdosage (5)(6)(7)(8)(9)(10).…”

Section: History Of Beta-2 Agonistsmentioning

confidence: 99%

Beta-2 agonist discussions in asthma and a review of current data

Erdinç

2011

Tuberk Toraks

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ÖZET Astımda beta-2 agonist tartışmaları ve mevcut verilere bakış Güncel kılavuzlar doğrultusunda astım tedavisinde kontrol edici olarak ilk seçenek inhale steroidlerdir. Bununla birlikte özellikle hava yolu obstrüksiyonu bulunan pek çok hastada gerek semptom giderici olarak, gerekse ek kontrol edici ilaç olarak hava yolu düz kaslarında relaksasyona yol açan bronkodilatörlere ihtiyaç duyulmaktadır. Hem kısa etkili hem de uzun etkili beta-2 agonistler (SABA ve LABA) astımda kullanılan bronkodilatörler arasında ayrı bir öneme sahiptir. İyi bilinen yararlarına rağmen, son yıllarda LABA'ların güvenliliği üzerine artan sayıda makale yayınlanmıştır. Bununla beraber, LABA monoterapisi ile ilişkili olduğu bildirilen risk artışı, standart tedavi olarak LABA ile kombine inhale kortikosteroid alan hastalarda gözlenmemiştir. Astım mortalitesi dahil olmak üzere, riskler ile ilgili tartışma sürerken, inhale kortikosteroide LABA eklenmesinin yararları geniş şekilde dokümante edilmiştir. Farmakogenetik gelişmeler sayesinde, birçok çalışmada etkinlik ve güvenliliği gösterilmiş olan bu ilaçların bazı istenmeyen yan etkilerinin potansiyel genetik temeli olabileceğine de dikkat çekilmiştir. Sonuç olarak; LABA'lar inhale kortikosteroidler ile birlikte kullanıldığında, astımda semptomların giderilmesi ve akciğer fonksiyonlarının iyileştirilmesinde etkili ve güvenlidir; ancak, inhale kortikosteroid tedavisi yokluğunda LABA monoterapisi hiçbir şekilde uygulanmamalıdır. Uygun dozlarda inhale kortikosteroid kullanımı-na rağmen kurtarma tedavisine gereksinim duyan astım hastalarının tedavi rejimlerine düzenli bronkodilatör eklenmelidir.Anahtar Kelimeler: Astım, kısa etkili beta-2 agonist, uzun etkili beta-2 agonist, inhale steroid. SUMMARY Beta-2 agonist discussions in asthma and a review of current dataMünevver ERDİNÇ Department of Chest Diseases, Faculty of Medicine, Ege University, Izmir, Turkey. Current guidelines recommend inhaled steroids as the first line control medication in the treatment of asthma. However, many patients particularly with airway obstruction need bronchodilators either as a symptom reliever or control medicati- Yazışma Adresi (Address for Correspondence):Dr. Münevver ERDİNÇ, Ege Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, 35100, Bornova, İZMİR -TURKEY e-mail: munevver.erdinc@ege.edu.tr Current guidelines recommend inhaler steroids as the first line control medication in the treatment of asthma. However, many patients particularly with airway obstruction need bronchodilators either as symptom reliever or control medication to provide relaxation of bronchiolar smooth muscles (1). Beta-2 agonists are of particular importance among the bronchodilators used in asthma.In the recent years, a growing body of publications has been published on the safety of long acting beta-2 agonists (LABA). This article will provide a brief definition of LABA and short acting beta-2 agonist (SABA) followed by an assessment of the process with LABAs and a discussion of most recent data (2). HISTORY of BETA-2 AGONISTSEpi...

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Prescribed Fenoterol and Death From Asthma in New Zealand, 1981-83; Case-Control Study

Cited by 539 publications

References 17 publications

A Case-control Study of Asthma Death and Life-threatening Attack: Their Possible Relationship with Prescribed Drug Therapy in Japan.

A Case-control Study of Asthma Death and Life-threatening Attack: Their Possible Relationship with Prescribed Drug Therapy in Japan.

Differential Effects of .BETA.2-Adrenoceptor Desensitization on the IgE-Dependent Release of Chemical Mediators from Cultured Human Mast Cells

Beta-2 agonist discussions in asthma and a review of current data

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