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Biomedical subjects

Krishnan Parameswaran

Publications and source records attributed to Krishnan Parameswaran.

9 recordsLinked to original sources
PubMed2004

Leukotriene receptor antagonists for allergic rhinitis: a systematic review and meta-analysis.

PURPOSE: To compare the clinical efficacy of leukotriene receptor antagonists with that of placebo, antihistamines, and nasal corticosteroids in patients with allergic rhinitis or nasal polyposis. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials of the effectiveness of leukotriene receptor antagonists in patients with rhinitis. Composite daily rhinitis symptom scores (as a percentage of the maximum score) and rhinitis-specific quality of life (unit scores ranging from 0 to 6) were pooled after assessing heterogeneity among studies. The pooled estimates were expressed as weighted mean differences between treatments in a random-effects model. We considered a difference of 10% in nasal score and 0.6 units in quality-of-life score to be clinically relevant. RESULTS: Of the 196 citations, 11 studies on seasonal allergic rhinitis were used in the analysis: eight evaluating leukotriene receptor antagonists alone or in combination with other treatments versus placebo or other treatments (n = 3924) and three evaluating leukotriene receptor antagonists plus an antihistamine (n = 80). Leukotriene receptor antagonists reduced mean daily rhinitis symptom scores (in absolute terms) 5% (95% confidence interval [CI]: 3% to 7%) more than did placebo. However, antihistamines improved the nasal symptoms score 2% (95% CI: 0% to 4%) more than did leukotriene receptor antagonists, and nasal corticosteroids improved the score 12% (95% CI: 5% to 18%) more than did leukotriene antagonists. Leukotriene receptor antagonists significantly improved rhinoconjunctivitis quality of life by 0.3 units (95% CI: 0.24 to 0.36 units) when compared with placebo. There were no randomized controlled trials evaluating the effect of leukotriene receptor antagonists on perennial allergic rhinitis or polyposis. CONCLUSION: Leukotriene receptor antagonists are modestly better than placebo, as effective as antihistamines, but less effective than nasal corticosteroids in improving symptoms and quality of life in patients with seasonal allergic rhinitis.

Drug Therapy, Combination↗
PubMed2004

The effect of pranlukast on allergen-induced bone marrow eosinophilopoiesis in subjects with asthma.

We investigated the mechanisms by which leukotriene receptor antagonists decrease airway eosinophil number. In a randomized, double-blind crossover study, we examined the effects of 2 weeks of treatment with pranlukast 300 mg twice a day or placebo on allergen-induced changes in airway eosinophil number and bone marrow eosinophil progenitors in 15 subjects with mild asthma. Pranlukast treatment for 2 weeks decreased mean sputum eosinophil count from 0.15 x 10(6)/g (5.3% of cells) before treatment to 0.02 x 10(6)/g (0.7% of cells) after treatment (p < 0.05), whereas placebo did not. Pranlukast also decreased the eosinophil count (5.6% at 7 hours and 7.5% at 24 hours) (p < 0.05) after allergen inhalation compared with placebo (13.8% at 7 hours and 15.3% at 24 hours). There was a similar trend for sputum cells immunostaining for EG2, eotaxin, interleukin-5, and regulated upon activation, normal T cell expressed and secreted. Pranlukast also significantly attenuated the allergen-induced increase in the number of bone marrow eosinophil/basophil cfu (mean 0.3) at 24 hours compared with placebo (mean 6.2). The proportion of CD34(+) cells expressing the eotaxin receptor CC chemokine receptor 3, 24 hours after allergen inhalation, was also reduced by pranlukast. We conclude that, the cysteinyl leukotriene receptor antagonist, pranlukast, attenuates allergen-induced increase in airway eosinophils by decreasing bone marrow eosinophilopoiesis and airway chemotactic and eosinophilopoietic cytokines.

Adult↗
PubMed2003

Inhaled corticosteroids for asthma: common clinical quandaries.

This narrative review provides evidence-based explanations to some of the common clinical concerns regarding inhaled corticosteroids. Inhaled corticosteroids are the treatment of choice for a newly diagnosed asthmatic patient. Better results are obtained when treatment is initiated as soon as the diagnosis is made. Asthma control can be achieved and maintained in most patients with a low or moderate dose of inhaled corticosteroid administered in two daily doses. Longer duration of treatment provides more sustained benefits than treatment that is intermittent and for short periods of time. The clinical benefits can be observed within 24 hours of commencing treatment and may be more pronounced in patients with an eosinophilic bronchitis. Inhaled corticosteroids provide additional benefit when used in conjunction with prednisone in acute severe asthma. Low doses do not have clinically deleterious side effects on the bones, growth, eye, or hypothalamo-pituitary-adrenal-axis. However, they do not normalize lung function and prevent structural changes in the airway wall in all asthmatic patients.

Administration, Inhalation↗
PubMed2002

Cysteinyl leukotrienes promote human airway smooth muscle migration.

Cysteinyl leukotrienes promote airway smooth muscle (ASM) contraction and proliferation. Little is known about their role in ASM migration. We investigated this using cultured human ASMs (between the second and fifth passages) obtained from the large airways of resected nonasthmatic lung. Platelet-derived growth factor-BB (1 ng/ml) promoted significant (3.5-fold) ASM migration of myocytes across collagen-coated 8- micro m polycarbonate membranes in Transwell culture plates. Leukotriene E(4) (10(-7), 10(-8), 10(-9) M) did not demonstrate a chemotactic effect; it did promote chemokinesis. Priming by leukotriene E(4) (10(-7) M) significantly augmented the directional migratory response to platelet-derived growth factor (1.5-fold, p < 0.05). This was blocked by montelukast (10(-6) M), demonstrating the effect to be mediated by the cysteinyl leukotriene receptor. The "priming effect" was also partially attenuated by prostaglandin E(2) (10(-7) M). Whereas both the chemokinetic and the chemotactic "primed" responses were equally attenuated by a p38 mitogen-activated protein kinase inhibitor (SB203580, 25 micro M) and by a Rho-kinase inhibitor (Y27632, 10 micro M), the chemotactic response showed greater inhibition than chemokinesis by a phosphatidylinositol-3 kinase inhibitor (LY294002, 50 micro M). These experiments suggest that cysteinyl leukotrienes play an augmentary role in human ASM migration. The phosphatidylinositol-3 kinase pathway is a key signaling mechanism in the chemotactic migration of ASM cells in response to cysteinyl leukotrienes.

Cell Movement↗
PubMed2002

The effect of cysteinyl leukotrienes on growth of eosinophil progenitors from peripheral blood and bone marrow of atopic subjects.

BACKGROUND: The accumulation of eosinophils into the peripheral blood and airways of asthmatic subjects is, in part, dependent on cysteinyl leukotrienes (cysLTs). However, the effect of cysLTs on peripheral blood and bone marrow eosinophil pro-genitor cells in allergic subjects is not known. OBJECTIVE: The purpose of this study was to evaluate the effects of leukotriene (LT) D(4) and LTE(4) and the cysLT(1) receptor antagonist montelukast on peripheral blood and bone marrow eosinophil-basophil progenitor growth and development in atopic subjects. METHODS: Semisolid methylcellulose cultures for peripheral blood and bone marrow eosinophil-basophil colonies were counted after incubation with or without addition of LTD(4), LTE(4), and montelukast in the presence of suboptimal concentrations of GM-CSF, IL-3, and IL-5. RESULTS: Peripheral blood eosinophil-basophil colony-forming unit cultures grown in the presence of GM-CSF and bone marrow eosinophil-basophil colony-forming units grown in the presence of IL-5 were significantly increased by the addition of LTD(4) (0.1 micromol/L). This increase was suppressed by montelukast (1 micromol/L). CONCLUSION: This study has demonstrated that the cysLT LTD(4) can stimulate proliferation of eosinophil hematopoietic progenitor cells in the presence of eosinophilopoietic cytokines. The suppressive effect by montelukast demonstrates that this is a cysLT(1) receptor-mediated effect.

Acetates↗
PubMed2002

Airway hyperresponsiveness and calcium handling by smooth muscle: a "deeper look".

We propose that abnormal calcium handling by the airway smooth muscle may be an important determinant of airway hyperresponsiveness. The amplitude, frequency, or localization of Ca(2+) oscillations in the smooth muscle may determine the degree of airway sensitivity and reactivity, which are characteristic features of asthma.

Asthma↗
PubMedDate not supplied

Clinical models to compare the safety and efficacy of inhaled corticosteroids in patients with asthma.

There is no consensus on the methods to compare the clinical efficacy of different inhaled corticosteroids. A comparison needs to be made in terms of relative potency, and studies should include two-, or preferably, three-dose comparisons. A number of clinical models and outcomes are available; they have their relative advantages and disadvantages. While measurements of symptoms and spirometry are easy and readily available, they show a flat dose-response relationship. Measurements of bronchial hyper-responsiveness to exercise and adenosine monophosphate, allergen-induced airway responses, and measurements of inflammation in sputum and exhaled air show steep dose-response relationships, particularly to low doses of inhaled steroids. An uncontrolled asthma model followed by stabilization with a short course of additional steroid, with measurements of airway responsiveness and airway inflammation, in a crossover study seems more promising than the other models. Drug deposition studies and mathematical modelling of drug pharmacokinetics in the airway may provide complementary information to clinical drug relative potency studies. Fine particle dose and emitted doses, rather than the nominal dose, should be considered in the estimation of clinical and systemic effects, respectively. When a second entry (generic) drug is being evaluated in comparison with the innovator drug (same compound and same device), it may be appropriate to consider accepting a generic as bioequivalent if it satisfies pharmaceutical equivalence.

Adrenal Cortex Hormones↗