B J Lipworth

..In conclusion, montelukast may be suitable as tailored second-line controller therapy instead of salmeterol in asthmatic children expressing the susceptible Arg(16) genotype, a move towards a personalized medicine approach to management...

..8). Thus, viewing the data as a whole, it would seem that, compared to CFC-BDP and alternative inhaled corticosteroids, HFA-BDP in a dose of up to 800 microg day(-1) exhibits a favourable therapeutic ratio...

..To determine whether genetic polymorphisms of the core promoter region of the 5-lipoxygenase gene contribute to the clinical response to leukotriene receptor antagonists...

..To study the effects of electrostatics in a plastic spacer on the lung deposition of salbutamol in asthmatic children...

..Prescribers of inhaled and intranasal corticosteroids should be aware of the potential for long term systemic effects. The safest way to use these drugs is to 'step-down' to achieve the lowest possible effective maintenance dosage...

..Her appearance, mental state, and myopathy also improved with no loss of asthma control. This case illustrates the potential for developing clinically relevant adverse effects of inhaled corticosteroids when given at licensed doses...

..There is controversy about the development of bronchodilator subsensitivity after regular administration of long-acting beta(2)-agonists...

..To compare the pharmacokinetic profile of Beclazone (beclomethasone dipropionate) in its chlorofluorocarbon (CFC)-based and CFC-free formulations...

..To appraise the data on systemic adverse effects of inhaled corticosteroids...

..Genetic polymorphism determines agonist-induced down-regulation and desensitization of beta2-adrenoceptors...

..Ciclesonide (hydrofluoroalkane propellant) is a novel inhaled corticosteroid with few, if any, clinical adverse events...

..To examine the relationship between changes in quality of life and measures of lung function and bronchial hyper-responsiveness (BHR) during treatment with high-dose inhaled corticosteroids in patients with uncontrolled asthma...

..Objective: To evaluate the methacholine bronchoprotection afforded by formoterol, 12 microg, delivered via Clickhaler and Aerolizer dry powder inhalers and a pressurized metered-dose inhaler (pMDI) in mild-to-moderate asthmatic patients...

..Bronchial hyperresponsiveness to adenosine monophosphate, an indirect measure of airway inflammation, is a sensitive marker of inhaled corticosteroid efficacy...

..Ultimately, clinicians will want to know whether PDE4 inhibitors are anything more than expensive "designer" theophylline, the archetypal non-selective phosphodiesterase inhibitor...

..CONCLUSIONS: Montelukast and salmeterol exhibited significant improvements in asthma control when given as second-line therapy. Montelukast also produced significant effects on AMP challenge and EOS suggesting anti-inflammatory activity...

..36). CONCLUSIONS: Both treatments were effective in managing allergic rhinitis symptoms, and patients' symptoms were more closely associated with domiciliary measurements of nasal flow than laboratory measurements of nasal function...

..Sputum markers tend to be more sensitive than blood when assessing the anti-inflammatory response...

..Similar improvements in AHR and recovery time were observed following both indirect bronchoconstrictor stimuli...

..This suggests that the greater glucocorticoid potency of HFA-FP may be offset by the greater lung bioavailability of HFA-BDP...

..There is little data comparing their effects on inflammation. We have evaluated the effects of HFA-BDP and CFC-BDP on pulmonary and systemic markers of asthmatic inflammation...

..Asthma and allergic rhinitis are manifestations of a single unified allergic airway, for which the best treatment is uncertain...

..Further studies are required to evaluate the relationship between inhaled mannitol and other surrogate inflammatory markers...

..Both treatments significantly reduced allergic rhinitis symptoms...

..Elite swimmers have high rates of rhinoconjunctivitis and exercise-induced bronchoconstriction. Moreover, exposure to chlorine and chlorine metabolites is known to induce bronchial hyper-reactivity...

..The homozygous glycine-16 polymorphism of the beta(2)-adrenoceptor occurs in approximately 40% of patients and is known to predispose to agonist-induced downregulation and desensitization...

..We conducted a dose ranging study in asthma and persistent allergic rhinitis to evaluate if intranasal corticosteroids exhibit a sparing effect on the dose of inhaled corticosteroid...

..Further studies are now required to assess the potential role for BB as either monotherapy in milder patients or add-on therapy in more severe asthmatics...

..Further studies are required to evaluate whether these effects of montelukast translate into clinical benefits...

..Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents an interesting model to investigate the existence of a non-allergic unified airway. The factors associated with airway dysfunction in CRSwNP are not fully understood...

..Current asthma guidelines recommend step-down of inhaled corticosteroids (ICS) to the minimum dose required for control of symptoms...

..These results show that sublingual administration of salbutamol tablet has no clinical benefit over the oral route...

..CONCLUSIONS: Combination inhalers improve pulmonary function without potentiating anti-inflammatory effects on exhaled NO and serum ECP as compared with ICS alone, but delay acute salbutamol recovery after bronchoconstriction...

..The present results would therefore suggest that CIC might confer a better therapeutic ratio than FP when used at higher doses...

..Further work is required to confirm that this is also true in the most severe cases, and the available evidence needs to be put into guidelines and implemented...

..If a spacer is required for reasons other than increasing delivered drug dose, then the addition of a readily available cardboard tube will fulfill many of the required functions with no expense to the patient...

..At 1000 micro g/day there was increased systemic bioactivity with BEC-HFA compared with FLU-HFA, without any gain in airway efficacy...

..Nasal lysine-aspirin challenge appeared to be a reproducible and safe method in assessing patients with aspirin-induced asthma...

..CONCLUSION: BB and FEX, in comparison to PL, were equally effective in attenuating the nasal response to AMP and in improving nasal symptoms, highlighting a potential role for BB in the treatment of allergic rhinitis...

..CONCLUSION: Fexofenadine did not affect recovery to a fixed dose of AMP challenge or any other surrogate inflammatory markers when given as add-on therapy to corticosteroid-treatedatopic asthmatic patients...

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..A study was undertaken to evaluate the Arg-16 and Gly-16 genotypes for the acute salbutamol response following methacholine bronchial challenge between the first and last doses of formoterol (FM) and salmeterol (SM) combination inhalers...

..This suggests that a very little of the labelled nebulised dose is respirable. Other factors such as patient preference, cost and compliance will determine the inhaler device that is chosen...

..However, further long-term studies will be required to study their comparative effects on nasal symptoms, quality of life, as well as on nasal inflammatory cells...

..End-organ hyperreactivity is an important feature of the allergic airway. There are no data directly comparing the responsiveness to treatment of different nasal provocation tests (NPT)...

..The aim of this proof-of-concept study was to assess whether nasal adenosine monophosphate (AMP) challenge may be used to quantify dose response to topical fluticasone propionate (FP) in persistent allergic rhinitis (PER)...

..Addition of salmeterol/tiotropium to half the dose of fluticasone afforded small, but significant improvements in pulmonary function. These effects were not associated with commensurate changes in subjective symptoms or quality of life...

..Longer-term studies are indicated to evaluate their relative efficacy on asthma exacerbations...

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..Our aim is to evaluate whether responsiveness to leukotriene receptor antagonists was determined by expression of the variant (C) or wild-type (A) polymorphism of this enzyme...

..This may explain the beneficial effects of combination inhalers on exacerbations...

..Supplementation with potassium and magnesium had no effect on electrocardiographic changes, and the addition of triamterene to bendrofluazide only attenuated electrocardiographic responses in some subjects...

..8 doubling dose/dilution shift. This stabilizing effect on airway smooth muscle may explain their beneficial effects on exacerbations...

..This further supports their application as surrogate inflammatory markers for therapeutic trials in allergic rhinitis, potentially as 20 min challenges which can be conducted in a non-hospital setting...

..DL was 0.1 (-0.6-0.8) and 0.1 (-0.2-0.3), respectively. CONCLUSIONS: Recommended once daily doses of fexofenadine and desloratadine were equally effective in improving nasal peak flow and nasal symptoms in SAR...

..This in turn suggests an association between allergen exposure and AMP responsiveness in asthmatics. Further prospective long-term evaluation is indicated to assess whether allergen avoidance strategies can modify the airway response...

..Further studies are indicated to evaluate the long-term add-on effects of FEX on asthma exacerbations...

..Thus, extrafine particle formulations of inhaled corticosteroids are of clinical interest...

..The lower thresholds are suitable for monitoring response to therapy, and they expose patients to significantly less provocation agent...

..Further studies are indicated to assess whether ML confers additional benefits to FEX in SAR...

..To compare a test version of HFA fluticasone/salmeterol (FP/SM) combination inhaler (Neolab, UK) with the reference product Seretide (GlaxoSmithKline, UK)...

..The relationship between beta2-adrenoceptor polymorphisms and bronchoprotective response with long-acting beta2-adrenoceptor agonists is unknown...

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..CONCLUSIONS: This study has indicated therefore, that Aerodose Inhaler is approximately five times as efficient as the Pari LC Plus and Evohaler in relative lung delivery of salbutamol in moderate to severe asthmatics...

..It would therefore make more sense to first of all optimize the dose of anti-inflammatory therapy with inhaled corticosteroid and to then consider adding a long-acting beta2-adrenoceptor agonist for patients who are poorly controlled...

..Thus, optimizing the dose of inhaled corticosteroid as monotherapy would seem to be the logical first step, which is in keeping with current guidelines...

..Thus, assessing lung function may miss potentially beneficial anti-inflammatory effects of montelukast when used as add-on therapy...

..CONCLUSIONS: BB exhibited protection against AMP-induced nasal responsiveness during the grass pollen season in sensitized patients. This is turn may explain its potential clinical efficacy in patients with SAR...

..Consequently it is suggested that potassium or tremor responses may be used to evaluate the relative lung delivery of salbutamol from different inhaler devices...

..Here I overview the clinical pharmacology of leukotriene antagonists and appraise the published data from clinical trials, and look at the appropriate position of these agents in asthma management guidelines...

..24 vs 4.85. Thus, parameters of beta 2-AR function are unaltered in asthmatic patients who have not been exposed to beta 2-agonists, suggesting that asthma is not associated with an endogenous defect of beta 2-AR...

..These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs...

..Our data refute the assertion that MF has negligible systemic bioavailability and a lower potential for systemic adverse effects compared with FP...

..Aside from patients with known aspirin-sensitive asthma, physicians have avoided the use of aspirin in asthmatic patients in general because it was believed that this agent might precipitate worsening of their condition...

..Although HFA-FP had fewer systemic effects than CFC-FP at 1,000 microg/d, there was no benefit to increasing HFA-FP to > 500 microg/d...

..Long-term studies are required to evaluate whether these improvements on surrogate inflammatory markers translate into commensurate reductions in airway remodelling and exacerbations...

..05) of overnight urinary cortisol/creatinine and serum osteocalcin. CONCLUSION: Once-daily inhaled corticosteroid and leukotriene antagonist improved the primary outcome variable of bronchial hyperresponsiveness to a similar degree...

..There are few reports of calculated MCIDs in the Rhinology literature...

..These results show that the hypokalaemic response to terbutaline was additive to that of frusemide, and that triamterene attenuated the hypokalaemic response to frusemide, but not terbutaline...

..We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting beta(2) agonists...

..08 to 1.42) and 2.16 (95% confidence interval 1.88 to 2.44) shift, respectively. CONCLUSIONS: High doses of inhaled corticosteroids conferred greater improvements in bronchial hyperresponsiveness than low doses...

..CONCLUSION: It may not be possible to use the McKenzie vasoconstrictor assay to predict which patients are most or least susceptible to inhaled corticosteroids for anti-asthmatic efficacy or systemic adverse effects...

..Impulse oscillometry (IOS) and body plethysmography (PLETH) are more sensitive than spirometry to assess inhaled therapies in COPD...

..There were significant (P < 0.05) improvements in nasal symptoms and quality of life. CONCLUSIONS: AMP nasal challenge using acoustic rhinometry may be a useful test to assess short-term treatment response in patient with PAR...

..Further studies are indicated to evaluate the longer-term effects of levocetirizine on asthma exacerbations...

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..Instrument fixation or examiner performed test is also preferable to allowing the patient to position the probe. The repeatability of the probe-stand method was similar to the examiner-performed method...

..Our objective was to study the role of FLG null alleles in asthma exacerbations...

..CONCLUSION: Higher expression of CD45 and CD45RO by eosinophils from asthmatic patients appeared to be a consequence of asthma rather than atopy and further supports a role for activated eosinophils in asthma...

..In conclusion, montelukast may be a useful therapeutic option in addition to standard therapy (i.e. intra-nasal corticosteroids or anti-histamines) when treating patients with chronic rhinosinusitis in a real life clinical setting...

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..For the patient whose lung function is less impaired, with evidence of ongoing BHR where bronchoprotection is needed (e.g. exercise, allergen, cold air), or when there is concomitant allergic rhinitis, then an LTA would be more suitable...

..Data for in vitro binding affinity do not therefore translate into commensurate differences in in vivo bioactivity at clinically recommended doses...

..85 doubling dose shift (95% confidence interval, 0.69 to 1.02). CONCLUSION: Since the estimated protection amounted to almost one doubling dose, this reinforces the role of LTRAs as anti-inflammatory therapy in asthma...

..03): 6.92 vs 5.72 (95% CI on the difference: 0.12, 2.29). CONCLUSIONS: Severe COPD patients who are receiving high dose FP are susceptible to the development of systemic adverse effects, irrespective of the presence of emphysema...

..Further studies are indicated to evaluate whether montelukast exhibits additive effects to ICS/long-acting beta2-adrenoceptor agonist combination inhalers upon clinically important outcomes...

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..Using cyclodextrin with budesonide enables it to be formulated in a solution for nebulization...

..In asthmatic patients receiving long-term inhaled corticosteroid therapy, there are concerns regarding the potential for developing systemic adverse effects on bone metabolism, possibly even in the absence of adrenal suppression...

..6. Exercise hyperkalaemia was blunted significantly by C400 and C800 in comparison with all doses of atenolol and nadolol.(ABSTRACT TRUNCATED AT 250 WORDS)..