Challenges of treating asthma in people who smoke.
ABSTRACT Cigarette smoking is common in asthma and is associated with poor symptom control and a reduced therapeutic response to inhaled and oral corticosteroids as compared with nonsmokers with asthma. This review examines the range of adverse health effects of smoking in asthma, the inflammatory mechanisms that may influence the efficacy of current drugs and discusses potential future therapeutic directions.
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ABSTRACT: In developed countries approximately one-quarter of adults with asthma are active cigarette smokers. These individuals have poorly controlled symptoms, impaired therapeutic responses to corticosteroids, and increased rates of health care utilization compared to nonsmokers with asthma. Persistent airflow obstruction can develop in asthma, particularly in smokers. Accelerated loss of lung function in adulthood as well as genetic, environmental risk factors (other than smoking), and submaximal lung growth in childhood may also contribute to the development of persistent airflow obstruction in smokers with asthma. The best strategy for managing symptoms due to persistent airflow obstruction in smokers with asthma is uncertain and, in particular, which recommendations from international guidelines for asthma or COPD are most appropriate for the management of this patient group.
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ABSTRACT: In a previous study, we reported a new pyrroloquinazoline derivative, 3-(4'-acetoxy-3',5'-dimethoxy)benzylidene-1,2-dihydropyrrolo[2,1-b]quinazoline-9-one (PQ), which inhibited human purified 5-lipoxygenase activity and prostaglandin E2 release in lipopolysaccharide-stimulated RAW 264.7 cells. In the present work, we show that PQ inhibits cyclo-oxygenase-2 activity in intact cell assays (human monocytes) and purified enzyme preparations (ovine isoenzymes) without affecting cyclo-oxygenase-1 activity. This behaviour was confirmed in vivo by using the zymosan-injected mouse air pouch model, where PQ caused a marked reduction in cell migration and leukotriene B4 levels at 4 h, as well as inhibition of prostaglandin E2 levels without affecting cyclo-oxygenase-2 expression at 24 h after zymosan stimulation. In addition, oral administration of this compound significantly reduced carrageenan-induced mouse paw oedema and phenyl-p-benzoquinone-induced writhings in mice. These results indicate that oral PQ exerts analgesic and anti-inflammatory effects, which are related to dual inhibition of cyclo-oxygenase-2 and 5-lipoxygenase activities.European Journal of Pharmacology 02/2002; 434(3):177-85. DOI:10.1016/S0014-2999(01)01539-4 · 2.68 Impact Factor
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ABSTRACT: Dendritic cells (DCs) are crucial for the processing of antigens, T lymphocyte priming and the development of asthma and allergy. Smokers with asthma display altered therapeutic behaviour and a reduction in endobronchial DC CD83 expression compared with non-smokers with asthma. No information is available on the impact of smoking on peripheral blood DC profiles. Determine peripheral blood DC profiles in subjects with and without asthma with differing smoking histories. Forty-three asthmatics (17 smokers, nine ex-smokers and 17 never-smokers) and 16 healthy volunteers (nine smokers and seven never-smokers) were recruited. Spirometry, exhaled nitric oxide and venesection was performed. DC elution was by flow cytometry via the expression of DC surface markers [plasmacytoid (pDC) (BDCA-2, CD303), type 1 conventional (cDC) (BDCA-1, CD1c), and type 2 cDC (BDCA-3, CD141)]. Subjects with asthma displayed increases in all DC subtypes compared with normal never-smokers: [type 1 cDCs - asthma [median% (IQR)]: 0.59% (0.41, 0.74), normal never-smokers: 0.35% (0.26, 0.43), P=0.013]; type 2 cDCs - asthma: 0.04% (0.02, 0.06), normal never-smokers: 0.02% (0.01, 0.03), P=0.008 and pDCs - asthma: 0.32% (0.27, 0.46), normal never-smokers: 0.22% (0.17, 0.31), P=0.043, and increased pDC and type 1 cDCs compared with normal smokers. Smoking did not affect DC proportions in asthma. Cigarette smoking reduced pDC proportions in normal subjects [normal never-smokers: 0.22% (0.17, 0.31); normal smokers: 0.09% (0.08, 0.15), P=0.003]. This study shows for the first time that subjects with asthma display a large increase in peripheral blood DC proportions. Cigarette smoking in asthma did not affect the peripheral blood DC profile but did suppress pDC proportions in non-asthmatic subjects. Asthma is associated with a significant increase in circulating DCs, reflecting increased endobronchial levels and the importance of DCs to the development and maintenance of asthma. (Clinical trials.gov identifier: NCT00411320)Clinical & Experimental Allergy 02/2011; 41(5):665-72. DOI:10.1111/j.1365-2222.2010.03692.x · 4.32 Impact Factor