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Comparable reductions in hyperpnoea-induced bronchoconstriction and markers of airway inflammation after supplementation with 6·2 and 3·1 g/d of long-chain n-3 PUFA in adults with asthma.
Williams, NC, Hunter, KA, Shaw, DE, Jackson, KG, Sharpe, GR, Johnson, MA
The British journal of nutrition. 2017;(10):1379-1389
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Abstract
Although high dose n-3 PUFA supplementation reduces exercise- and hyperpnoea-induced bronchoconstriction (EIB/HIB), there are concurrent issues with cost, compliance and gastrointestinal discomfort. It is thus pertinent to establish the efficacy of lower n-3 PUFA doses. Eight male adults with asthma and HIB and eight controls without asthma were randomly supplemented with two n-3 PUFA doses (6·2 g/d (3·7 g EPA and 2·5 g DHA) and 3·1 g/d (1·8 g EPA and 1·3 g DHA)) and a placebo, each for 21 d followed by 14 d washout. A eucapnic voluntary hyperpnoea (EVH) challenge was performed before and after treatments. Outcome measures remained unchanged in the control group. In the HIB group, the peak fall in forced expiratory volume in 1 s (FEV1) after EVH at day 0 (-1005 (sd 520) ml, -30 (sd 18) %) was unchanged after placebo. The peak fall in FEV1 was similarly reduced from day 0 to day 21 of 6·2 g/d n-3 PUFA (-1000 (sd 460) ml, -29 (sd 17) % v. -690 (sd 460) ml, -20 (sd 15) %) and 3·1 g/d n-3 PUFA (-970 (sd 480) ml, -28 (sd 18) % v. -700 (sd 420) ml, -21 (sd 15) %) (P<0·001). Baseline fraction of exhaled nitric oxide was reduced by 24 % (P=0·020) and 31 % (P=0·018) after 6·2 and 3·1 g/d n-3 PUFA, respectively. Peak increases in 9α, 11β PGF2 after EVH were reduced by 65 % (P=0·009) and 56 % (P=0·041) after 6·2 and 3·1 g/d n-3 PUFA, respectively. In conclusion, 3·1 g/d n-3 PUFA supplementation attenuated HIB and markers of airway inflammation to a similar extent as a higher dose. Lower doses of n-3 PUFA thus represent a potentially beneficial adjunct treatment for adults with asthma and EIB.
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Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.
Chung, EH, Jia, Y, Ohnishi, H, Takeda, K, Leung, DY, Sutherland, ER, Dakhama, A, Martin, RJ, Gelfand, EW
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2014;(3):211-216.e1
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Abstract
BACKGROUND Numbers of CD8(+) T cells expressing the leukotriene B4 (LTB4) receptor, BLT1, have been correlated with asthma severity. OBJECTIVE To examine the activation and numbers of BLT1-expressing peripheral blood CD4(+) and CD8(+) T cells from patients with steroid-sensitive (SS) and steroid-resistant (SR) asthma. METHODS CD4(+) and CD8(+) T cells isolated from peripheral blood of healthy human subjects and patients with SS and SR asthma were stimulated in culture with anti-CD3/anti-CD28 followed by analysis of BLT1 surface expression and cytokine production. Activation of CD8(+) T cells after ligation of BLT1 by LTB4 was monitored by changes in intracellular Ca(2+) concentrations. RESULTS The number of BLT1-expressing cells was larger in patients with asthma than in controls and larger on activated CD8(+) than on CD4(+) T cells. Addition of LTB4 to activated CD8(+) T cells resulted in increases in intracellular Ca(2+) concentrations. Expansion of activated CD4(+) T cells, unlike CD8(+) T cells, was significantly decreased in the presence of corticosteroid. In patients with SS asthma, numbers of BLT1-expressing CD8(+) T cells were lower in the presence of corticosteroid, unlike in those with SR asthma in whom cell expansion was maintained. Levels of interleukin-13 were highest in cultured CD8(+) T cells, whereas interleukin-10 levels were higher in CD4(+) T cells from controls and patients with SS asthma. Interferon-γ levels were lowest in patients with SR asthma. CONCLUSION Differences in BLT1 expression, steroid sensitivity, and cytokine production were demonstrated in T lymphocytes from patients with SS and SR asthma. The LTB4-BLT1 pathway in CD8(+) cells may play an important role in asthma and serve as an important target in the treatment of patients with SR asthma.
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Effect of inhaled endotoxin on regional particle deposition in patients with mild asthma.
Bennett, WD, Herbst, M, Zeman, KL, Wu, J, Hernandez, ML, Peden, DB
The Journal of allergy and clinical immunology. 2013;(3):912-3
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[Administration of budesonide (inhaled steroid) to children to control intermittent asthma].
Ponce Castro, H, Rodríguez Espino, S, Rodríguez Orozco, AR
Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993). 2009;(1):9-12
Abstract
BACKGROUND Intermittent asthma in children is often treated only with short-action beta-agonists; however, most cases do not control totally the disease. OBJECTIVE To assess the effect of salbutamol, as rescue drug, associated with other drugs for controlling asthma. PATIENTS AND METHODS Fifty children, from 1 to 14 years old, with intermittent asthma, who were assisted at Out-Patient Consultation of Pediatric Allergy, Children Hospital Eva Samano de Lopez Mateos, from January to October, 2004, were selected. Treatment consisted of the following regimens: (1) salbutamol, (2) salbutamol and budesonide, (3) salbutamol and montelukast and (4) salbutamol, budesonide and montelukast. After three months of treatment asthma control degree was measured by disappearing of symptoms (total control) or decrease of symptoms in more than 70% a week (partial control). RESULTS A better control was observed in patients receiving budesonide (inhaled steroid) and salbutamol (p < 0.05), compared to those who were not treated with inhaled steroid. This regimen achieved in 44% the disappearing of symptoms (total control) and in 56% reduced the symptoms in more than 70% (partial control). Group receiving salbutamol, budesonide and montelukast reached a total and partial control in 47.1% and 52.9%, respectively. CONCLUSIONS Inhaled steroids are a choice to better control and avoid the progression of intermittent asthma. The use of new progression markers of asthma should be evaluated, in order to determine which children may receive early inhaled steroids and how long.
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Montelukast in asthma treatment in Croatia.
Samarzija, M, Jakopović, M, Pavicić, F, Kukulj, S, Popović-Grle, S, Beg-Zec, Z
Collegium antropologicum. 2005;(2):683-8
Abstract
The aim of this study was to determine the efficacy and safety of montelukast added to previous medication in the treatment of a mild and moderate asthma. Data were obtained via questionnaires given to the physicians and given further to their patients. Patients were divided in two groups, first followed 4 weeks (612 patients) and second followed 8 weeks (91 patients). We found out that there was a significant improvement in FEV1 (forced expiratory volume in first second) and general condition of patients and decreased number of salbutamol inhalations after using montelukast. In the second group of patients we find out the same significant improvement in FEV1, general condition and decrease in salbutamol inhalations after 4 weeks of using montelukast and further improvement after the next month of therapy. We conclude that montelukast is an efficient drug with little side effects and with a good compliance. Montelukast managed to achieve a good asthma control; therefore it has a significant place in asthma therapy.
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Factors affecting the efficiency of aerosol therapy with pressurised metered-dose inhalers through plastic spacers.
Chuffart, AA, Sennhauser, FH, Wildhaber, JH, ,
Swiss medical weekly. 2001;(1-2):14-8
Abstract
AIM: The main objective of this study was to compare the in vitro delivery of salbutamol from a chlorofluorocarbon(CFC)-propelled pressurised metered-dose inhaler (pMDI) versus a newly developed hydrofluoroalkane(HFA)-propelled pMDI through various spacers. In addition, we aimed to study the effect on bronchodilator response when using an optimal pMDI/spacer combination for aerosol delivery compared to a suboptimal combination. METHODS Particle size distribution and output from salbutamol pMDIs containing either CFC propellants (Ventolin) or HFA propellants (Airomir) were measured using a multistage liquid impinger (MSLI) and compared to that through both detergent-coated (non-static) or untreated (static) large volume (Nebuhaler, Volumatic) and small volume (Aerochamber) plastic spacers. Flow-volume curves (FEV1) were obtained from twelve asthmatic children with known significant bronchodilator response (8 males), aged 13-17 years, randomly inhaling salbutamol from a CFC-pMDI through a static spacer (Nebuhaler) and from an HFA-pMDI through a non-static spacer (Nebuhaler). RESULTS In vitro output of particles in the respirable range (< 6.8 microns) from HFA-pMDIs was significantly higher than that from CFC-pMDIs using various spacers. Removal of electrostatic charge increased output from CFC- and HFA-pMDIs through all spacers by 17-82%. The mean (SD) bronchodilator response after inhalation of salbutamol from a CFC-pMDI through a static spacer was 7.1% (6.3%) compared to 17.5% (7.9%) after inhalation from an HFA-pMDI through a non-static spacer (p = 0.002). CONCLUSIONS Use of a newly developed HFA-propelled pMDI greatly improves drug delivery through spacers compared to a CFC-propelled pMDI. However, electrostatic charge in plastic spacers remains the key determinant limiting delivery of salbutamol from a pMDI through spacers, and can be reduced by soaking the spacer in a household detergent. Using an optimal pMDI/spacer combination leads to a significantly improved bronchodilator response.
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[Expression of adhesion molecules LFA-1 (CD11a and ICAM-1 (CD54) on lymphocytes and chemokines IL-8 and MCP-1 concentrations in bronchoalveolar lavage of patients with asthma or chronic obstructive pulmonary disease].
Jahnz-Rózyk, K, Chciałowski, A, Pirozyńska, E, Rogalewska, A
Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego. 2000;(52):649-52
Abstract
Chemokines and cellular adhesion molecules are crucial determinants of the migration of immune effector cells to the tissues asthma and chronic obstructive pulmonary disease (COPD) are a complex of conditions, which have airflow limitation in common. The aim of this study was to determine the numbers and percentages of lymphocytes expressing adhesion molecules: LFA-1, ICAM-1 together with assessment of chemokines concentrations: IL-8 and MCP-1 in bronchoalveolar lavage fluid (BAL) of patients with asthma or chronic obstructive pulmonary disease (COPD). 12 patients with asthma, 14 patients with COPD, and 6 subjects of control group took part in this study. The expression of LFA-1 and ICAM-1 was assessed on lymphocytes by using immunohistochemistry (streptavidyn-biotin, DAKO, Denmark). ELISA test was used to measure IL-8 and MCP-1 concentrations in BAL (kits from R&D, USA). The percentage of lymphocytes expressing LFA-1 and ICAM-1 were: 33.9 +/- 23.8% and 25.8 +/- 12.2% in COPD patients, 23.9 +/- 12.1% and 15.3 +/- 4.42% in asthma patients, and 14.2 +/- 10% and 5.2 +/- 1.6% in the control group respectively. There was observed significant difference between the percentage of lymphocytes expressing LFA-1 and ICAM-1 of COPD and the control group. The concentrations of IL-8 were: 2306 +/- 1501 pg/ml in COPD, 233 +/- 27.3 pg/ml in asthma and 64 +/- 28.7 in the control group (p < 0.05). The concentrations of MCP-1 were: 768.9 +/- 668.1 pg/ml in COPD, 126.8 +/- 30.8 pg/ml in asthma, and 83.0 +/- 16.4 pg/ml in the control group (p < 0.05). There was observed correlation between lymphocytes expressing LFA-1 and IL-8 concentration (r = +0.5, p < 0.05) and between lymphocytes expressing LFA-1 and MCP-1 concentration (r = +0.5, p < 0.05), and between lymphocytes expressing ICAM-1 and MCP-1 concentration (r = +0.4, p < 0.05) only in COPD patients. Our data suggest that LFA-1 and ICAM-1 are important molecules in the recruitment of leukocytes and together with IL-8 and MCP-1 may have a role in pathomechanism of inflammation in asthma and especially in COPD.
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Fluticasone propionate/salmeterol combination provides more effective asthma control than low-dose inhaled corticosteroid plus montelukast.
Nelson, HS, Busse, WW, Kerwin, E, Church, N, Emmett, A, Rickard, K, Knobil, K
The Journal of allergy and clinical immunology. 2000;(6):1088-95
Abstract
BACKGROUND Asthma is a disease of chronic inflammation and bronchoconstriction. Inhaled corticosteroids (ICSs) provide important anti-inflammatory treatment but may not provide optimal control of asthma when taken alone. Two therapeutic alternatives for enhanced asthma control are to substitute the combination of fluticasone propionate (FP) and salmeterol (FP/Salm Combo) through the Diskus inhaler or to add montelukast to existing ICS therapy. OBJECTIVE We compared the efficacy and safety of FP/Salm Combo through the Diskus inhaler versus montelukast added to FP (FP + montelukast) in patients whose symptoms were suboptimally controlled with ICS therapy. METHODS We performed a multicenter, double-blind, double-dummy, parallel-group, 12-week study in 447 patients with asthma who were symptomatic at baseline while receiving low-dose FP. Patients were treated for 12 weeks with one of the following: (1) combination of FP 100 microg plus salmeterol 50 microg twice daily through the Diskus inhaler, or (2) FP 100 microg twice daily through the Diskus inhaler plus oral montelukast 10 mg once daily. RESULTS FP/Salm Combo treatment provided better overall asthma control than FP + montelukast with significantly greater improvements in morning peak expiratory flow (+24.9 L/min vs +13.0 L/min, P <.001), evening peak expiratory flow (+18.9 L/min vs +9.6 L/min, P <.001), and forced expiratory volume in 1 second (+0.34 L vs +0.20 L, P <.001), as well as a change in the percentage of days with no albuterol use (+26.3% vs +19.1%, P =.032) and the shortness of breath symptom score (-0.56 vs -0.40, P =.017). The groups had comparable improvements in chest tightness, wheeze, and overall symptom scores. Asthma exacerbation rates were significantly lower (P =.031) in the FP/Salm Combo group (4 patients, 2%) than in the FP + montelukast group (13 patients, 6%). Adverse event profiles were comparable. CONCLUSION Symptomatic patients on low-dose ICS therapy had significantly greater improvement in asthma control when switched to the FP/Salm Combo than when montelukast was added to ICS therapy.