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Latest Research on Asthma
     
Curr Opin Allergy Clin Immunol. 2008 Apr;8(2):163-7.
Long-term effects of asthma medications in children.
Tamesis GP, Covar RA.
Department of Pediatrics, National Jewish Medical and Research Center, Denver, Colorado, USA.

PURPOSE OF REVIEW: This review describes recent studies in children that evaluated long-term outcomes of controller asthma medications. RECENT FINDINGS: The literature is replete with studies demonstrating the immediate profound effects of inhaled corticosteroids on symptom control, reduction in morbidity and mortality rates, improvement in lung function, bronchial hyperresponsiveness, and inflammatory markers. Recent evidence supports that even this most effective class of medication does not alter the progression of recurrent wheeze to asthma, and that its effects on decline in lung function are limited. The lack of evidence supporting the superiority of lower dose inhaled corticosteroids combined with a long-acting beta-agonist over a full dose inhaled corticosteroid with respect to long-term efficacy measures and growth effects suggests that monotherapy with acceptable inhaled corticosteroid dose is the preferred treatment in children with mild to moderate persistent asthma. Montelukast has been shown to significantly reduce asthma exacerbations and lower use of supplemental inhaled corticosteroids compared with placebo. SUMMARY: There is mounting evidence that the currently available medications for childhood asthma have a substantial impact on multiple dimensions of asthma control. No drug in our current armamentarium, however, has been found to alter the natural progression of childhood asthma nor halt progressive airway damage in the more susceptible children.

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Curr Opin Allergy Clin Immunol. 2008 Apr;8(2):158-162.
Management of asthma in preschool children with inhaled corticosteroids and leukotriene receptor antagonists.
Bacharier LB.
Department of Pediatrics, Division of Allergy and Pulmonary Medicine, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, Missouri, USA.

PURPOSE OF REVIEW: The aim of this article is to review the recently published studies addressing various treatment approaches for asthma in preschool children. RECENT FINDINGS: The heterogeneity of wheezing in the preschool years complicates the study of asthma in this age group. Once children at highest risk for persistence of wheezing are identified, various management strategies may be thoroughly studied. Several recent studies have confirmed the efficacy and safety of both inhaled corticosteroids and leukotriene receptor antagonists in the management of early childhood asthma. In addition to examining clinical efficacy, studies investigating the effects of these treatment modalities on the underlying airway inflammation have recently increased in number and quality and confirm the anti-inflammatory actions of these therapeutic strategies in the preschool child with asthma. SUMMARY: Evidence for the preferred treatment strategies for persistent asthma in young children remains incomplete. Based on the current body of evidence, there is rationale for further investigation of these management strategies, including direct comparisons between inhaled corticosteroids and leukotriene receptor antagonists, as well as the role of long-acting beta-agonists, potentially targeting the subpopulations of early childhood with wheezing who are at highest risk for persistence of asthma symptoms.

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Clin Rev Allergy Immunol. 2008 Apr;34(2):205-16.
Exercise-induced Bronchospasm In Children.
Randolph C.
Center for Allergy, Asthma, Immunology, 1389 West Main Street, Suite 205, Waterbury, CT, 06708, USA, ccrandmd@aol.com.

This review will encompass definition, history, epidemiology, pathogenesis, diagnosis, and management of exercise -induced bronchospasm in the pediatric individual with and without known asthma. Exercise induced asthma is the conventional term for transient airway narrowing in a known asthma in association with strenuous exercise usually lasting 5-10 minutes with a decline in pulmonary function by at least 10%. Exercise induced asthma will be referred to as exercise induced bronchospasm in an asthmatic. Exercise-induced bronchospasm (EIB ) is the same phenomenon in an individual without known asthma. EIB can be seen in healthy individuals including children as well as defense recruits and competitive or elite athletes. The diagnosis with objective exercise challenge methods in conjunction with history is delineated. Management is characterized with pharmacotherapy and non pharmacotherapeutic measures for underlying asthma as well as exercise induced bronchospasm and inhalant allergy. Children can successfully participate in all sports if asthma is properly managed.

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Pneumologie. 2008 Mar;62(3):170-6.
[Effects of high altitude on bronchial asthma]
[Article in German]
Schultze-Werninghaus G.
Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil, Zentrum der Inneren Medizin, Medizinische Klinik III, Pneumologie, Allergologie, Schlaf- und Beatmungsmedizin, Bochum. gerhard.schultze-werninghaus@rub.de

Sojourns in the high mountains have been recommended to patients with asthma for many decades. It is the aim of this contribution to summarise the published studies about the effects of a stay at > 1500 m above sea level on asthmatic patients. These data from 428 adolescent and adult patients indicate an improvement of asthma symptoms and lung function during sojourns at high altitude. In many patients a reduction of the steroid therapy was achievable. Profound changes in the immune system have been demonstrated at high altitude, with a reduction of B- and T-helper cell activation. Total and mite-specific immunoglobulin E antibodies decrease significantly during longer sojourns. These changes are associated with a reduction of airway inflammation (e. g., reduction of eosinophil activation, NO exhalation and bronchial hyper-responsiveness). The fact that also patients with non-allergic asthma demonstrate a reduction of their airway inflammation at high altitude suggests that the high altitude climate has beneficial effects on asthma beyond the effects of allergen avoidance. High UV exposure and low humidity could be important additional factors, to explain the reductions in asthma severity in the high mountain climate. Larger controlled studies should be performed to prove the positive effects of the high altitude climate on asthma.

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Prim Care Respir J. 2008 Mar 12 [Epub ahead of print]
Alcohol-based pressurised metered-dose inhalers for use in asthma: a descriptive study.
Alrasbi M, Sheikh A.
Hon. Clinical Research Assistant, Allergy & Respiratory Research Group, Division of Community Health Sciences: GP Section, University of Edinburgh, Scotland, UK.

BACKGROUND: Chlorofluorocarbons (CFCs) have historically served as the propellants of choice in pressurised metered-dose asthma inhalers, but concern has been raised in recent decades regarding their damaging effect on the ozone layer. Among the alternative propellants being considered is alcohol, which can be used as a co-solvent in asthma inhalers. Healthcare professionals need to be aware of alcohol-containing inhalers, since certain populations may have religious and/or cultural concerns regarding the use of such preparations. OBJECTIVES: To identify pressurised metered-dose asthma inhalers which contain alcohol-based propellants. METHODS: We searched the British National Formulary to identify companies that manufacture asthma treatments and wrote to them to enquire about which of their products contained alcohol and if so in what percentage. These direct contacts were supplemented by searching medical databases and the Internet for additional information. RESULTS: We identified 11 manufacturers of asthma inhalers, seven of which produced pressurised metered-dose inhalers; of these, six were willing to disclose the requested information, and information on the seventh product was obtained from an alternative valid source of information. Most CFC preparations contain alcohol, but CFC- and alcohol-free preparations do exist. CONCLUSIONS: Clinicians need to be aware that the majority of CFC-free inhalers contain alcohol. Alcohol-free, and CFC- and alcohol-free, preparations are available for the delivery of both rescue and preventative treatment and these should be considered for use in those patients who may have concern about alcohol-based treatments.

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Allergy Asthma Proc. 2008 Mar 11 [Epub ahead of print]
The impact of home cleaning on quality of life for homes with asthmatic children.
Barnes C, Kennedy K, Gard L, Forrest E, Johnson L, Pacheco F, Hu F, Amado M, Portnoy J.

Treatment with common household bleach containing hypochlorite destroys dust mites and denatures protein allergens. The purpose of this study was to determine if home use of hypochlorite products results in lowered exposure to bacteria, fungi, and protein allergens and improved quality of life (QOL) for asthmatic persons in the home. Asthmatic and nonasthmatic households containing at least three persons (between 2 and 17 years of age) were recruited. Households were supplied one of three sets of cleaning products (regular products, some containing hypochlorite; regular products plus three additional productswith dilute hypochlorite; control, no products). Participants were supplied with cleaning instructions and asthma education. The control group was instructed to clean as usual. Participants completed general health and QOL questionnaires. Asthmatic participants completed an additional asthma QOL questionnaire. Families participated in the study for 8 weeks and completed the full set of questions every 2 weeks. Homes were visited at the beginning of the study and twice thereafter at monthly intervals. Samples evaluated were surface bacteria, viable and nonviable airborne spores, and dust antigen content. Reductions in surface bacteria, airborne fungal spores, and dust antigen levels were achieved. Significant improvement in general health parameters was seen for the asthmatic product groups over the control group. Significant improvement in general QOL andasthma-specific QOL was seen in the asthmatic group. Emphasis on cleaning and cleaning education combined with hypochlorite-based cleaning supplies resulted in significantly improved QOL for families with asthmatic children.

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J Allergy Clin Immunol. 2008 Mar;121(3):607-13.
Natural history of asthma: persistence versus progression-does the beginning predict the end?
Panettieri RA Jr, Covar R, Grant E, Hillyer EV, Bacharier L.
Pulmonary, Allergy & Critical Care Division, University of Pennsylvania, Philadelphia, PA 19104-3403, USA. rap@mail.med.upenn.edu

Environmental exposures during the early years and airway obstruction that develops during this time, in conjunction with genetic susceptibility, are important factors in the development of persistent asthma in childhood. Established risk factors for childhood asthma include frequent wheezing during the first 3 years, a parental history of asthma, a history of eczema, allergic rhinitis, wheezing apart from colds, and peripheral blood eosinophilia, as well as allergic sensitization to aeroallergens and certain foods. Risk factors for the development of asthma in adulthood remain ill defined. Moreover, reasons for variability in the clinical course of asthma--persistence in some individuals and progression in others--remain an enigma. The distinction between disease persistence and disease progression suggests that these are different entities or phenotypes. There is currently no consensus on whether disease progression requires either airway inflammation or airway remodeling or the combination of the two. For patients with irreversible airway obstruction, inflammation might, in part, be necessary but perhaps not entirely sufficient to induce the irreversible component, some of which could be attributed to alterations in the structure of the bronchial wall. Intervening with intermittent or daily inhaled corticosteroids in high-risk infants and children does not prevent disease progression or impaired lung growth. These findings, however, might not apply to adults, and further study in adults is needed to determine the effect of inhaled corticosteroid therapy on disease progression.

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Prim Care Respir J. 2008 Feb;17(1):39-45.
Does continuous use of inhaled corticosteroids improve outcomes in mild asthma? A double-blind randomised controlled trial.
Reddel HK, Belousova EG, Marks GB, Jenkins CR.
Woolcock Institute of Medical Research and University of Sydney, Camperdown, New South Wales, Australia.

AIM: To compare the effects of fluticasone and placebo on asthma control in patients with mild asthma. METHOD: Adults with FEV1 >80% predicted and reliever use <2 times/week were randomised to receive fluticasone 250 mcg/day or placebo double-blind for 11 months. Exacerbations were treated with four weeks' fluticasone 500 mcg/day. Primary outcomes were electronically-recorded morning PEF and FEV1, analysed by mixed model regression. RESULTS: 44 subjects were randomised (23-fluticasone, 21-placebo). Fluticasone led to significantly better morning FEV1 (mean difference 5.4% predicted, p<0.0001), morning PEF, clinic spirometry, exhaled nitric oxide levels, and airway hyperresponsiveness, but there were no differences in reliever use, symptoms or quality of life. Fewer patients had mild exacerbations on fluticasone (22% vs 62%, p=0.02). CONCLUSION: The goals of asthma treatment include not only control of symptoms, but also prevention of future adverse outcomes such as exacerbations - which can occur even in mild asthma. This study showed that treatment with low dose inhaled corticosteroids led to significant improvements in lung function, exacerbations, and in pathophysiological predictors of future risk, even though symptoms were minimal at entry. For patients with mild asthma, discussion about treatment needs to consider not only short-term benefit, side effects and cost, but also long-term reduction of risk. This study was completed prior to mandatory registration for clinical trials.

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Free Radic Res. 2008 Jan;42(1):94-102.
Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: proof of concept.
Wood LG, Garg ML, Powell H, Gibson PG.
Department of Respiratory and Sleep Medicine, Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia. lisa.wood@newcastle.edu.au

Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.

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Acta Biomed. 2007 Dec;78(3):233-45.
Inhalatory therapy training: a priority challenge for the physician.
Melani AS.
Respiratory Physiopathology and Rehabilitation, Cardiothoracic Department, Polyclinic Le Scotte, Azienda Ospedaliera Universitaria Senese, Siena, Italy. a.melani@ao-siena.toscana.it

Patients with asthma and COPD commonly use inhaled drugs. The 3 types of currently available devices for inhaled therapy (Metered-dose inhaler, dry powder inhaler, and nebulizer) are clinically equivalent. However, since many different inhalers are available for inhaled therapy, the choice of the delivery device is important for optimizing the results of aerosol therapy.Traditional press-and-breathe Metered Dose Inhalers (pMDIs) have recently improved their ecological appeal, can be used in every clinical and environmental situation, their dosing is convenient and highly reproducible, but their efficient delivery remains highly technique dependent. Poor inhalation technique can be minimised by the use of add-on valved holding chambers, which are seldom used in the clinical practice possibly because they are cumbersome. Breath Actuated devices (BAIs), such as Dry Powder Inhalers (DPIs), which are environmental-friendly, safe, effective, reliable, portable and self-contained, overcome problems of handbreath co-ordination associated with pMDIs usage, but their use is also undermined by common errors of inhalation technique in real life. Nebulizers are cumbersome and time-comsuming for use and maintenance, but their use needs less cooperation than inhalers. Although nebulizer practice is not always evidence-based, some patients, mainly elderly prefer nebulizers for regular long-term usage. Despite the introduction of newer devices, clear advantages of a particular delivery system over other inhalers in terms of compliance, preference, and cost-effectiveness are not currently available. The objective of an ideal and easy-to use inhaler is far from reality. Patient education is the critical factor in the use and misuse of delivery devices and effectiveness of aerosol therapy. The choice of the device has to be tailored according to the patient's needs, situation, and preference.Whatever the chosen inhaler, education from health caregivers has a key-role for improving inhaler technique and compliance. Differences among delivery devices represent another challenge to patient use and caregiver instruction.

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J Community Health Nurs. 2007 Winter;24(4):237-51.
Development, implementation and evaluation of a new adult asthma self-management program.
Tousman S, Zeitz H, Taylor LD, Bristol C.
Department of Health Psychology, Jefferson College of Health Sciences, Roanoke, VA 24031, USA. stousman@jchs.edu

The purpose of the research was to develop, implement, and evaluate a new adult asthma self-management program with a multidisciplinary perspective. Small groups of adults met for 2 hr for 7 consecutive weekly meetings. Participants were asked to practice asthma specific behaviors (including peak expiratory flow monitoring, avoidance/removal of asthma triggers, and controller medication adherence) and general lifestyle behaviors (including drinking water, practicing relaxation, washing hands, and exercising). Learner-centered teaching techniques such as interactive communication and social support were utilized to help participants practice self-management behaviors including problem-solving and goal-setting. Paired sample t-tests included statistically significant improvements in asthma knowledge, asthma specific quality of life (QOL), asthma specific behaviors such as peak flow monitoring and general life style behaviors such as frequency of daily exercise. These results provide evidence that this new adult asthma self-management program can lead to both knowledge acquisition and behavioral changes.

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J Investig Allergol Clin Immunol. 2007;17(6):399-405.
Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing.
Moreno-Ancillo A, Moreno C, Ojeda P, Domínguez C, Barasona MJ, García-Cubillana A, Martín S.
Hospital Virgen del Puerto, Plasencia, Spain.

OBJECTIVE: The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerance of once-daily sublingual immunotherapy without updosing. Reduction in symptoms and medication use was the primary endpoint. METHODS: One hundred five patients with rhinitis and/or asthma due to grass and olive sensitization were randomized to be treated with placebo or active sublingual immunotherapy with the SLITone grass mix plus olive pollen extract for 6 months before the 2005 pollen season. Patients recorded symptoms and medication intake for 8 weeks during the pollen seasons in 2004 (n=37) and 2005 (n=85). RESULTS: Allergic symptoms were significantly decreased in the active immunotherapy group (P = .004) but not in the placebo group. There were no differences in scores between groups during the 2005 pollen season. Subjective assessments on a visual analog scale and a quality-of-life questionnaire indicated an improvement in actively treated patients with significant differences in both symptoms and medication use (P = .006). The rate of systemic adverse reactions was comparable in the 2 groups. No anaphylactic or severe adverse reactions were reported. Local adverse reactions, which were more common in the active immunotherapy group, were mostly immediate, were limited to the lips and mouth, and did not require treatment. CONCLUSION: Once-daily sublingual immunotherapy without updosing was well tolerated. The actively treated patients showed a significant reduction in symptom and medication scores and an improvement in their quality of life although there were no significant differences between the groups probably due to the low allergen season in which the study was evaluated.

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Environ Health Perspect. 2007 Dec;115(12):1691-5.
A systematic review and meta-analysis of interventions used to reduce exposure to house dust and their effect on the development and severity of asthma.
MacDonald C, Sternberg A, Hunter PR.
School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, United Kingdom.

OBJECTIVES: We assessed whether any household dust reduction intervention has the effect of increasing or decreasing the development or severity of atopic disease. DATA SOURCES: Electronic searches on household intervention and atopic disease were conducted in January 2007 in EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials. No date or language restriction was placed on the literature search. DATA EXTRACTION: We included randomized controlled trials comparing asthma outcomes in a household intervention group with either placebo intervention or no intervention. DATA SYNTHESIS: Fourteen studies met the inclusion criteria. Eight recruited antenatally and measured development of atopic disease. Six recruited known atopic individuals and measured disease status change. Meta-analyses on the prevention studies found that the interventions made no difference to the onset of wheeze but made a significant reduction in physician-diagnosed asthma. Meta-analysis of lung function outcomes indicated no improvement due to the interventions but found a reduction in symptom days. Qualitatively, health care was used less in those receiving interventions. However, in one study that compared intervention, placebo, and control arms, the reduction in heath care use was similar in the placebo and intervention arms. CONCLUSIONS: This review suggests that there is not sufficient evidence to suggest implementing hygiene measures in an attempt to improve outcomes in existing atopic disease, but interventions from birth in those at high risk of atopy are useful in preventing diagnosed asthma but not parental-reported wheeze.

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Pediatr Pulmonol. 2007 Dec 17;43(2):179-186 [Epub ahead of print]
Effects of montelukast on subjective and objective outcome measures in preschool asthmatic children.
Moeller A, Lehmann A, Knauer N, Albisetti M, Rochat M, Johannes W.
Swiss Pediatric Respiratory Research Group, Division of Respiratory Medicine, University Children's Hospital Zurich, Zürich, Switzerland.

It is well accepted that control of airway inflammation is crucial for overall asthma control. Hence, efficient anti-inflammatory therapy is important for disease control. Therefore, we studied the effect of a treatment with montelukast on subjective and objective measures in preschool asthmatic children with insufficient control of airway inflammation, illustrated by increased fractional exhaled nitric oxide (FeNO). Thirty-one preschool children (2.5-5 years) were included in this study. Children with FeNO >/= 10 ppb at the first visit received montelukast 4 mg as a first line therapy or an add-on therapy to their baseline treatment (group 1). Therapy was not changed at first visit in children with FeNO < 10 ppb (group 2). Symptom scores, FeNO, lung function (forced oscillation, Rrs8Hz) and airway responsiveness to adenosine 5'-monophosphate (AMP) were assessed at visits 1 and 2 eight weeks apart. There was a significant decrease in FeNO (median [interquartile range]; 12.9 [3.7] vs. 7.6 [6.85] ppb, P = 0.011), Rrs8Hz (mean +/- SD; 10.03 +/- 3.1 vs. 8.72 +/- 2.43 hPa.s/L; P = 0.047) and symptom scores (2[2] vs. 1.5[2], P = 0.034) and a significant increase in the provocative AMP dose (2.65 +/- 2.1 vs. 4.54 +/- 1.05; P = 0.015) in group 1 but not in group 2. First line or add-on treatment of oral montelukast in preschool children with mild to moderate asthma and elevated FeNO, decreased levels of FeNO, improved airway responsiveness to AMP, lung function and symptom scores. Pediatr Pulmonol. 2008; 43:179-186. (c) 2007 Wiley-Liss, Inc.

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Respir Med. 2007 Dec 13 [Epub ahead of print]
Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD.
Lavorini F, Magnan A, Christophe Dubus J, Voshaar T, Corbetta L, Broeders M, Dekhuijzen R, Sanchis J, Viejo JL, Barnes P, Corrigan C, Levy M, Crompton GK.
Unità Funzionale di Medicina Respiratoria, Università Degli Studi di Firenze, Italy.

BACKGROUND: Incorrect usage of inhaler devices might have a major influence on the clinical effectiveness of the delivered drug. This issue is poorly addressed in management guidelines. METHODS: This article presents the results of a systematic literature review of studies evaluating incorrect use of established dry powder inhalers (DPIs) by patients with asthma or chronic obstructive pulmonary disease (COPD). RESULTS: Overall, we found that between 4% and 94% of patients, depending on the type of inhaler and method of assessment, do not use their inhalers correctly. The most common errors made included failure to exhale before actuation, failure to breath-hold after inhalation, incorrect positioning of the inhaler, incorrect rotation sequence, and failure to execute a forceful and deep inhalation. Inefficient DPI technique may lead to insufficient drug delivery and hence to insufficient lung deposition. As many as 25% of patients have never received verbal inhaler technique instruction, and for those that do, the quality and duration of instruction is not adequate and not reinforced by follow-up checks. CONCLUSIONS: This review demonstrates that incorrect DPI technique with established DPIs is common among patients with asthma and COPD, and suggests that poor inhalation technique has detrimental consequences for clinical efficacy. Regular assessment and reinforcement of correct inhalation technique are considered by health professionals and caregivers to be an essential component of successful asthma management. Improvement of asthma and COPD management could be achieved by new DPIs that are easy to use correctly and are forgiving of poor inhalation technique, thus ensuring more successful drug delivery.

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Chest. 2007 Dec;132(6):1876-81.
Effects of montelukast treatment and withdrawal on fractional exhaled nitric oxide and lung function in children with asthma.
Montuschi P, Mondino C, Koch P, Ciabattoni G, Barnes PJ, Baviera G.
Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo F. Vito, 1, 00168 Rome, Italy. pmontuschi@rm.unicatt.it.

BACKGROUND: Leukotriene receptor antagonists (LTRAs) reduce fractional exhaled nitric oxide (Feno) concentrations in children with asthma, but the effect of LTRA withdrawal on Feno and lung function is unknown. We aimed to study the effect of treatment and withdrawal of montelukast, a LTRA, on airway inflammation as reflected by Feno and lung function in children with asthma. METHODS: A double-blind, randomized, placebo controlled, parallel group study was undertaken in 14 atopic children with mild persistent asthma who were treated with oral montelukast (5 mg/d for 4 weeks) and 12 atopic children with mild persistent asthma who received matching placebo. A follow-up visit was performed 2 weeks after montelukast or placebo withdrawal. RESULTS: Montelukast reduced Feno concentrations by 17% (p = 0.067), an effect that was more pronounced (35%) [p = 0.0029] when children with seasonal atopy who were exposed to relevant allergens during the treatment phase were excluded from analysis (n = 3). Compared to those at the end of treatment, Feno concentrations were increased 2 weeks after montelukast withdrawal (p = 0.023) concomitant with a reduction in absolute FEV(1) values (p = 0.011), FEV(1) percentage of predicted values (p = 0.006), FEV(1)/FVC ratio (p = 0.002), and forced expiratory flow at 25% to 75% of FVC values (p = 0.021). These changes were not observed in the placebo group. CONCLUSIONS: LTRAs reduce Feno concentrations in children with asthma, and withdrawal can result in increased Feno values and worsening of lung function in children with asthma.

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J Allergy Clin Immunol. 2007 Dec;120(6):1269-75.
Time for a paradigm shift in asthma treatment: from relieving bronchospasm to controlling systemic inflammation.
Bjermer L.
Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden. leif.bjermer@med.lu.se

Inflammation is a key pathology in asthma. In the central airways local inflammation leads to irreversible remodeling and airway dysfunction. Complex inflammatory changes also occur in the nose, sinuses, and small airways. In particular, rhinitis and asthma are linked by a common pathogenic process with common inflammatory cells, mediators, and cytokines. Cross-communication between the airways and bone marrow through inflammatory mediators in the circulation leads to systemic propagation of airway inflammation. Treatment of asthma has traditionally focused on relieving bronchospasm with beta(2)-agonists, which do not affect inflammation. Treatment of eosinophilic inflammation in the central airways with inhaled corticosteroids reduces local inflammation and improves pulmonary function but does not improve the systemic manifestations of asthma. If asthma is a systemic disease, the underlying systemic pathology should be targeted by identifying common disease mediators, mechanisms, or both that are triggered only during active disease. Of currently available therapies, leukotriene receptor antagonists block the action of cysteinyl leukotrienes and thus improve both asthma and rhinitis and other conditions systemically linked with asthma. Other potential treatments include receptor-blocking molecules and synthesis inhibitors related to eicosanoid inflammation. Treatment of asthma as a systemic disease requires clinical trials that evaluate the effects of new treatments on both lung function and the wider systemic pathology.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD001281.
Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma.
Tee A, Koh M, Gibson P, Lasserson T, Wilson A, Irving L.

BACKGROUND: Theophylline and long acting beta-2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles. OBJECTIVES: To assess the comparative efficacy, safety and side-effects of long-acting beta-2 agonists and theophylline in the maintenance treatment of adults and adolescents with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers. Most recent search: November 2006. SELECTION CRITERIA: All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-2 agonist. DATA COLLECTION AND ANALYSIS: In original review, two reviewers independently assessed trial quality and extracted data, similarly in this update two reviewers undertook this. Study authors were contacted for additional information. MAIN RESULTS: Thirteen studies with a total of 1344 participants met the inclusion criteria of the review. They were of varying quality. There was no significant difference between salmeterol and theophylline in FEV(1) predicted (6.5%; 95% CI -0.84 to 13.83). However, salmeterol treatment led to significantly better morning PEF (mean difference 16.71 L/min, 95% CI 8.91 to 24.51) and evening PEF (mean difference 15.58 L/min, 95% CI 8.33 to 22.83). Salmeterol also reduced the use of rescue medication. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Participants taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% CI 0.30 to 0.63, Risk Difference -0.11; 95% CI -0.16 to -0.07, Numbers Needed to Treat (NNT) 9; 95% CI 6 to 14). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.50; 95% CI 0.29 to 0.86, Risk Difference -0.07; 95% CI -0.12 to -0.02, NNT 14; 95% CI 8 to 50) and gastrointestinal adverse events (Relative Risk 0.30; 95% CI 0.17 to 0.55, Risk Difference -0.11; 95% CI -0.16 to -0.06, NNT 9; 95% CI 6 to 16). AUTHORS' CONCLUSIONS: Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

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Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000195.
Corticosteroids for preventing relapse following acute exacerbations of asthma.
Rowe B, Spooner Ch, Ducharme F, Bretzlaff J, Bota G.

BACKGROUND: Acute asthma is responsible for many emergency department (ED) visits annually. Between 12 to 16% will relapse to require additional interventions within two weeks of ED discharge. Treatment of acute asthma is based on rapid reversal of bronchospasm and reducing airway inflammation. OBJECTIVES: To determine the benefit of corticosteroids (oral, intramuscular, or intravenous) for the treatment of asthmatic patients discharged from an acute care setting (i.e. usually the emergency department) after assessment and treatment of an acute asthmatic exacerbation. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register and reference lists of articles. In addition, authors of all included studies were contacted to locate unpublished studies. The most recent search was run in October 2006. SELECTION CRITERIA: Randomized controlled trials comparing two types of corticosteroids (oral, intra-muscular, or inhaled) with placebo for outpatient treatment of asthmatic exacerbations in adults or children. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Six trials involving 374 people were included. One study used intramuscular corticosteroids, five studies used oral corticosteroids. The review was split into two reviews and although the latest search yielded no additional placebo controlled trials an additional IM study was included.Significantly fewer patients in the corticosteroid group relapsed to receive additional care in the first week (Relative risk (RR) 0.38; 95% confidence interval (CI) 0.2 to 0.74). This favourable effect was maintained over the first 21 days (RR 0.47; 95% CI 0.25 to 0.89) and there were fewer subsequent hospitalizations (RR 0.35; 95% CI 0.13 to 0.95). Patients receiving corticosteroids had less need for beta(2)-agonists (mean difference (MD) -3.3 activations/day; 95% CI -5.6 to -1.0). Changes in pulmonary function tests (SMD 0.045; 95% CI -0.47 to 0.56) and side effects (SMD 0.03; 95% CI -0.38 to 0.44) in the first 7 to 10 days, while rarely reported, showed no significant differences between the treatment groups. Statistically significant heterogeneity was identified for the side effect results; all other outcomes were homogeneous. From these results, as few as ten patients need to be treated to prevent relapse to additional care after an exacerbation of asthma. AUTHORS' CONCLUSIONS: A short course of corticosteroids following assessment for an asthma exacerbation significantly reduces the number of relapses to additional care, hospitalizations and use of short-acting beta(2)-agonist without an apparent increase in side effects. Intramuscular and oral corticosteroids are both effective.

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Arch Dis Child. 2007 Jul 18; [Epub ahead of print]
Daily versus As-Needed Inhaled Corticosteroid for Mild Persistent Asthma*
*The Helsinki Early Intervention Childhood Asthma Study.
Turpeinen MT, Nikander K, Pelkonen A, Syvänen P, Sorva R, Raitio H, Malmberg P, Juntunen-Backman K, Haahtela T.
Department of Allergy, Helsinki University Hospital, Finland.

OBJECTIVE: To compare inhaled budesonide given daily or as-needed in mild persistent childhood asthma. Patients, design and INTERVENTIONS: 176 children aged 5-10 years with newly detected asthma were randomized into three treatment groups: (1) continuous budesonide (400 microg twice daily for 1 month, 200 microg twice daily for Months 2-6, 100 microg twice daily for Months 7-18); (2) budesonide, identical treatment to Group 1 during Months 1-6, then budesonide for exacerbations as-needed for Months 7-18; and (3) disodium cromoglycate (DSCG) 10 mg three-times daily for Months 1-18. Exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. MAIN OUTCOME MEASURES: Lung function, the number of exacerbations and growth. RESULTS: Compared with DSCG the initial regular budesonide treatment resulted in a significantly better improvement of lung function, fewer exaxerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During Months 7-18 patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in Group 2 and 1.58 in Group 3. The number of asthma free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalized during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. CONCLUSIONS: Regular use of budesonide afforded better asthma control but more systemic effect than use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. A proportion of children does not seem to need continuous ICS treatment.

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Eur J Med Res. 2007 Jun 27;12(6):255-63.
Efficacy of the Combination of Fluticasone Propionate and Salmeterol in Patients with Moderate Persistent Asthma within a "Real-life" Setting.
Trautmann M, Banik N, Tews JT, Jörres RA, Nowak D.
Institute and Outpatient Clinic for Occupational and Environmental Medicine, Ludwig-Maximilians-University, Ziemssenstr. 1, 80336 Munich, Germany. dennis.nowak@med.uni-muenchen.de.

There are only few data on the effectiveness of recommended drug therapies in asthma under "real-life" conditions without targeted intervention. The study aimed at analyzing the efficacy of the fixed combination of the inhaled corticosteroid fluticasone propionate and the long-acting beta2-agonist salmeterol (FS) for maintenance treatment of moderate persistent asthma (GINA stage 3) within an observational design, mimicking "real-life" as closely as possible. The fixed combination was compared with other forms of treatment that were in accordance with treatment guidelines (pooled comparison (PC) group). Patients kept a diary during a 12-month observation period and routine visits were taken for surveillance. Among 596 patients, 371 patients belonged to the FS and 225 patients to the PC group. The proportion of symptom-free days (SFD) was higher in the FS than PC group (median, 76 vs 67%; p=0.002). Furthermore, the change in asthma control score (p<0.0001) and the percent increase in FEV1 (p<0.05) after 12 months were greater. There was a lower percentage of patients with hospital stays (p<0.05). The proportions of episode-free or sick-leave days and the number of routine or emergency visits did not significantly differ between groups. Direct costs of treatment per SFD were lower in the FS than PC group (median, 3.78 vs 4.41 Euro; p<0.05). We conclude that in a setup close to clinical practice treatment of patients with moderate persistent asthma with the fixed combination of fluticasone propionate and salmeterol has beneficial effects compared to other forms of therapy and can improve cost-efficiency.

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Isr Med Assoc J. 2007 Jun;9(6):472-5.
The beneficial effects of Xolair (omalizumab) as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available treatment (GINA 2002 step IV)—the Israeli arm of the INNOVATE study.
Sthoeger ZM, Eliraz A, Asher I, Berkman N, Elbirt D.
Department of Medicine B, Kaplan Medical Center, Rehovot, Israel.

BACKGROUND: Patients with severe persistent asthma despite GINA 2002 step 4 treatment are at risk for asthma-related morbidity and mortality. This study constitutes the Israeli arm of the international INNOVATE study. OBJECTIVES: To determine the efficacy and safety of Xolair as an add-on treatment in patients with severe persistent asthma. METHODS: Asthma patients (age 12-75 years) not controlled with high dose inhaled corticosteroids and long-active beta-2 agonists were randomized to receive either Xolair or placebo for 28 weeks in a double-blind study in two Israeli centers. RESULTS: Thirty-three patients, 20 females and 13 males, mean age 54 +/- 11.7 years, were included in the Israeli arm of the INNOVATE study. There were neither major adverse events nor withdrawals from the study. Xolair (omalizumab) significantly reduced the rate of clinically significant asthma exacerbations (55% reduction) and all asthma-related emergency visits (53% reduction). CONCLUSIONS: In patients with severe persistent difficult-to-treat asthma, despite regular treatment with LABA and inhaled corticosteroids (GINA 2002 step 4), Xolair is a safe and effective treatment.

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Adv Ther. 2007 May-Jun;24(3):463-77.
Evaluation of Albuterol 1.25 mg and 0.62 mg for Nebulization in 6- to 12-Year-Old Children With Moderately Severe Asthma.
Kemp J, Turck CJ, York JM.
Department of Pediatrics, Division of Immunology and Allergy, University of California at San Diego, California.

To assess the efficacy and safety of 2 different strengths of a manufactured albuterol solution for nebulization (AccuNeb(R); DEY, L.P., Napa, Calif), 349 children with moderate to severe asthma were enrolled in this prospective, multicenter, double-blind, placebo-controlled study. For 4 wk, children 6 to 12 y old were randomly assigned to 1.25 mg (A1) or 0.62 mg (A2) albuterol or placebo (P), nebulized 3 times daily for 4 weeks. Pulmonary function and safety were evaluated at weeks 0, 2, and 4 (visits 2-4). Nonparametric tests (Kruskal-Wallis and Wilcoxon's rank-sum) were used to compare treatments. Primary endpoint (week 4, %Delta area under the curve [AUC] forced expiratory volume in 1 sec [FEV(1)]) results for A1, A2, and P were 90.3%*h*, 73.6%*h*, and 34.2%*h. Secondary assessments for A1, A2, and P were as follows: (1) week 2, %DeltaAUC FEV1 (99.5%*h*, 104.5%*h*, and 43.6%*h(; (2) maximum FEV1 (28.6%*, 26.3%*, and 13.4%); and (3) duration of effect (116.8 min*, 115.9 min*, and 39.2 min). A2 was more effective in children 10 y of age or younger and in children 11 to 12 y of age who weighed </=40 kg or had less severe asthma; A1 was more effective in children 11 to 12 y of age who weighed >40 kg or had more severe asthma. Adverse events (occurring in 47% of children) were considered unrelated to drug treatment. Observations on electrocardiogram (notably QTc interval) were similar to those for placebo. A1 and A2 appeared effective in improving pulmonary function and were well tolerated in children aged 6 to 12 y.

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Int J Psychiatry Med. 2007;37(1):23-8.
Bupropion in the treatment of outpatients with asthma and major depressive disorder.
Brown ES, Vornik LA, Khan DA, Rush AJ.
Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, 75390-8849, USA. Sherwood.Brown@UTSouthwestern.edu

OBJECTIVE: Depressive disorders are common in asthma. Despite the high prevalence, antidepressant therapy in asthma patients with depression remains under-investigated. The objective of this pilot study was to investigate the use of bupropion for depression and anxiety in depressed asthma patients. METHOD: We conducted a 12-week open-label study of bupropion in 18 depressed asthma patients. Participants were assessed with the Hamilton Rating Scale for Depression (HAM-D-17), Hamilton Rating Scale for Anxiety (HAM-A), Inventory of Depressive Symptomatology--Self-Report (IDS-SR), Asthma Control Questionnaire (ACQ) and spirometry at baseline and weeks 1, 2, 4, 8, and 12. RESULTS: Significant baseline to exit improvements were observed on the HAM-D-17 (mean change = 4.72, SD = 7.78, p = 0.02) and the HAM-A (mean change = 2.12, SD = 3.97, p = 0.04). Based on the HAM-D-17 scores, 27.8% of the patients were responders and 16.7% were remitters. Significant correlations were found between changes in ACQ score and HAM-D-17 r = 0.73, p = 0.001), ACQ score and IDS-SR r = 0.58, = 0.012), and FEV1% Predicted and HAM-D-17 r = -0.66, p = 0.006). CONCLUSIONS: Bupropion treatment was associated with significant improvements in depression and anxiety symptoms in asthma patients. Improvements in asthma correlated significantly with improvements in depression.

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Respir Med. 2007 Apr 4; [Epub ahead of print]
Formoterol, montelukast, and budesonide in asthmatic children: Effect on lung function and exhaled nitric oxide.
Miraglia Del Giudice M, Piacentini GL, Capasso M, Capristo C, Maiello N, Boner AL, Capristo AF.
Dipartimento di Pediatria, Seconda Universita di Napoli, Napoli, Italy.

BACKGROUND: It has been proposed that asthma control may be achieved in part by minimizing airway inflammation. The simultaneous effects of inhaled steroids associated with long-acting beta-agonists and leukotriene antagonists on pulmonary function and airway inflammation are still largely unexplored in children with moderate persistent asthma. OBJECTIVES: The aim of this study was to investigate the effects of add-on therapy with long-acting beta-agonists and leukotriene antagonists on FEV(1) and exhaled nitric oxide levels (FE(NO)) in children. METHODS: Forty-eight steroid-naive atopic asthmatic children, 7-11 years of age, were randomly treated in four groups for two consecutive one-month periods, as follows: (1) first month: budesonide 200mug twice daily; second month: budesonide 400mug twice daily; (2) first month: budesonide 200mug twice daily+formoterol 9mug twice daily; second month: budesonide 200mug twice daily+montelukast 5mg once daily; (3) first month: budesonide 200mug twice daily+montelukast 5mg once daily; second month budesonide 200mug+formoterol 9mug twice daily; (4) first and second month: budesonide 400mug twice daily. RESULTS: All treatments resulted in a significant increase in lung function and a decrease in FE(NO) compared with values at baseline. Budesonide+montelukast in combination was the most effective treatment for reducing FE(NO) levels. CONCLUSION: This study demonstrates that add-on therapy with montelukast plus low-dose budesonide is more effective than the addition of long-acting beta-agonists or doubling the dose of budesonide for controlling FE(NO) in asthmatic children.

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Mayo Clin Proc. 2007 Apr;82(4):414-21.
Asthma treatment in a population-based cohort: putting step-up and step-down treatment changes in context.
Yawn BP, Wollan PC, Bertram SL, Lowe D, Butterfield JH, Bonde D, Li JT.
Department of Research, Olmsted Medical Center, 210 Ninth St SE, Rochester, MN 55904 USA. E-mail: Yawnx002@umn.edu.

OBJECTIVE: To assess the frequency and types of visits related to modifications in the intensity of asthma medications. PATIENTS AND METHODS: We retrospectively reviewed the medical records of adults (aged 18-40 years) and children (aged 6-17 years) living in Olmsted County, Minnesota, to evaluate changes in asthma medications by dose and drug class and site and type of visit (routine vs unscheduled) at the time of changes. All records from all visits were reviewed for each patient to identify asthma-related visits at all sites of care from January 1, 2002, through December 31, 2003. RESULTS: The study consisted of 397 adults and children. In 255 patients, 597 asthma medication changes occurred. Step-up changes usually occurred because of an exacerbation or loss of control of asthma and adhered to the medication hierarchy in the national asthma guidelines. Twenty step-up changes involved skipping inhaled corticosteroid (ICS) monotherapy and moving directly to combined ICSs plus a long-acting beta-agonist (LABA). Lack of documentation of asthma symptom frequency or interference with activities made it impossible to determine whether these 'skips' were appropriate. Only 78 physician-directed step-down changes were documented, usually to a lower dose of combined ICSs and LABAs or a move from combined ICSs and LABAs to anti-inflammatory monotherapy. Patients initiated additional step-down changes between encounters. Step-down changes occurred at routine or follow-up asthma visits, but the limited number of such visits provided few opportunities for step-down care. CONCLUSION: The continuing episodic-style treatment of asthma aimed at exacerbation management facilitates step-up changes in asthma therapy. The dearth of asthma evaluation visits limited opportunities to step down use of asthma medications and to provide long-term asthma management.

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J Allergy Clin Immunol. 2007 Apr 6; [Epub ahead of print]
Severe asthma in adults: What are the important questions?
Chanez P, Wenzel SE, Anderson GP, Anto JM, Bel EH, Boulet LP, Brightling CE, Busse WW, Castro M, Dahlen B, Dahlen SE, Fabbri LM, Holgate ST, Humbert M, Gaga M, Joos GF, Levy B, Rabe KF, Sterk PJ, Wilson SJ, Vachier I.
>From INSERM U454 and Clinique des Maladies Respiratoires, Montpellier.

The term severe refractory asthma (SRA) in adults applies to patients who remain difficult to control despite extensive re-evaluation of diagnosis and management following an observational period of at least 6 months by a specialist. Factors that influence asthma control should be recognized and adequately addressed prior to confirming the diagnosis of SRA. This report presents statements according to the literature defining SRA in order address the important questions. Phenotyping SRA will improve our understanding of mechanisms, natural history, and prognosis. Female gender, obesity, and smoking are associated with SRA. Atopy is less frequent in SRA, but occupational sensitizers are common inducers of new-onset SRA. Viruses contribute to severe exacerbations and can persist in the airways for long periods. Inflammatory cells are in the airways of the majority of patients with SRA and persist despite steroid therapy. The T(H)2 immune process alone is inadequate to explain SRA. Reduced responsiveness to corticosteroids is common, and epithelial cell and smooth muscle abnormalities are found, contributing to airway narrowing. Large and small airway wall thickening is observed, but parenchymal abnormalities may influence airway limitation. Inhaled corticosteroids and bronchodilators are the mainstay of treatment, but patients with SRA remain uncontrolled, indicating a need for new therapies.

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J Allergy Clin Immunol. 2007 Apr 6; [Epub ahead of print]
Achieving and maintaining asthma control in an urban pediatric disease management program: The Breathmobile Program.
Jones CA, Clement LT, Morphew T, Choi Kwong KY, Hanley-Lopez J, Lifson F, Opas L, Guterman JJ.
>From the Division of Allergy and Immunology; the Department of Pediatrics at the Los Angeles County+University of Southern California Medical Center and Keck School of Medicine at the University of Southern California.

BACKGROUND: National guidelines suggest that, with appropriate care, most patients can control their asthma. The probabilities of children achieving and maintaining control with ongoing care are unknown. OBJECTIVE: We sought to evaluate the degree to which children in a lower socioeconomic urban setting achieve and maintain control of asthma with regular participation in a disease management program that provides guideline-based care. METHODS: Interdisciplinary teams of asthma specialists use mobile clinics to offer ongoing care at schools and county clinics. A guideline-derived construct of asthma control is recorded at each visit. RESULTS: Two thousand one hundred eighty-five enrollees were eligible to evaluate the time to first achieve control, and 1591 patients were eligible to evaluate subsequent control maintenance. Depending on severity, 70% to 87% of patients with persistent asthma achieved control by visit 3, and 89% to 98% achieved control by visit 6. Subsequent control maintenance was highly variable. Thirty-nine percent of patients displayed well-controlled asthma (control at >90% of subsequent visits), whereas 13% displayed difficult-to-control asthma (<50% of subsequent visits). Patients from each baseline severity category were found in each group. Maintenance of control was influenced by physician-estimated compliance with the treatment plan, baseline severity, and the interval between clinic visits. CONCLUSIONS: Many children can achieve asthma control with regular visit intervals and guideline-based care; however, long-term control can be highly variable among patients in all severity categories. CLINICAL IMPLICATIONS: These findings highlight the need and feasibility for systematically tracking each patient's clinical response to individualize therapy and guide the use of population management strategies.

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Curr Med Res Opin. 2007 Apr;23(4):721-30.
Asthma control in patients with asthma and allergic rhinitis receiving add-on montelukast therapy for 12 months: a retrospective observational study.
Borderias L, Mincewicz G, Paggiaro PL, Guilera M, Sazonov Kocevar V, Taylor SD, Badia X.
Pneumology Department, San Jorge Hospital, Huesca, Spain.

BACKGROUND: Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma. OBJECTIVE: To evaluate asthma control and use of asthma-related medical resources by patients with inadequately controlled mild to moderate persistent asthma and seasonal AR who required addition of montelukast as part of routine care. METHODS: This multicenter, 24-month, pre-post retrospective observational study included patients receiving current inhaled corticosteroid (ICS) therapy (alone or in combination with long-acting beta-agonist [LABA]), who received add-on treatment with montelukast for 12 consecutive months. The incidence of asthma attacks, defined as emergency department visit, hospitalization, or oral corticosteroid use for asthma, was compared for the year before and the year after addition of montelukast to therapy. RESULTS: For the 696 patients from Italy, Poland, and Spain who were included in the analyses, the proportion of patients experiencing an asthma attack declined from 31.5% in the year before to 10.1% (p < 0.001) the year after addition of montelukast to therapy. Proportions of patients with an asthma-related emergency room visit, hospitalization, and oral corticosteroid use declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p < 0.01), respectively. The incidence of these outcomes declined in all three countries, regardless of baseline asthma severity or asthma therapy (ICS alone or ICS + LABA). Important study limitations include the possibility of selection bias or missing medical chart data in this retrospective study design. Also noteworthy is the inclusion of only those patients who remained persistent with montelukast therapy. Therefore, the results of the study are relevant for patients who remain persistent with montelukast therapy. CONCLUSIONS: Addition of montelukast to current ICS therapy improved long-term asthma control and resulted in substantial reductions in asthma-related resource use by patients with mild or moderate persistent asthma and concomitant seasonal AR who were persistent with montelukast therapy in this retrospective observational study.

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Paediatr Drugs. 2007;9(2):107-18.
Immunomodulatory effects of macrolide antibiotics in respiratory disease: therapeutic implications for asthma and cystic fibrosis.
Sharma S, Jaffe A, Dixon G.
Portex Unit, Institute of Child Health, London, UK.

The macrolide antibiotics are a family of related 14- or 15-membered lactone ring antibiotics. There has been recent interest in the beneficial effects of these drugs as immune modulators in respiratory conditions in children. Cystic fibrosis (CF) and asthma, both of which occur in childhood, have an underlying inflammatory component and are associated with significant morbidity. The pathogenesis of both conditions is poorly understood but several molecular mechanisms have been suggested.In CF, these mechanisms broadly involve altered chloride transport and alteration of the airway surface liquid with disordered neutrophilic inflammation. There is much evidence for a proinflammatory propensity in CF immune effector and epithelial cells and many studies indicate that macrolides modulate these inflammatory processes. Recent studies have confirmed a clinical improvement in CF following treatment with macrolides, but the exact mechanisms by which they work are unknown. Asthma is likely to represent several different phenotypes but in all of these, airway obstruction, bronchial hyperresponsiveness, and inflammation are central processes. Results from trials using macrolides have suggested an improvement in clinical outcome.The putative mechanisms of macrolide immunomodulatory action include improvement of the primary defense mechanisms, inhibition of the bacteria-epithelial cell interaction, modulation of the signaling pathway and chemokine release, and direct neutrophil effects. Putative mechanisms of phenotypic modulation have also been proposed involving interactions with nitric oxide, endothelin-1, and bronchoconstriction, endothelial growth factors and airway remodeling, and bioactive phospholipids in both CF and asthma.Further characterization of these effects and development of targeted designer drugs will further expand our therapeutic repertoire and lead to improved quality and quantity of life for patients with CF and asthma.

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Chest. 2007 Mar 30; [Epub ahead of print]
Internet based self-management offers an opportunity to achieve better asthma control in adolescents.
van der Meer V, van Stel HF, Detmar SB, Otten W, Sterk PJ, Sont JK.
Dept of Medical Decision Making and Dept of Public Health and Primary Care, Leiden University Medical Center.

BACKGROUND: Internet and short message service are emerging tools in chronic disease management of adolescents, but few data exist on barriers and benefits of internet-based asthma self-management. Our objective was to reveal perceived barriers and benefits by adolescents with well and poorly controlled asthma to current and internet-based asthma management. Methods Ninety-seven adolescents with mild to moderate persistent asthma monitored asthma control on a designated website. After four weeks 35 adolescents participated in eight focus groups. Participants were stratified on age, gender and asthma control level. We used qualitative and quantitative methods to analyze the written focus group transcripts. Results Limited self-efficacy to control asthma was a significant barrier to current asthma management in adolescents with poor asthma control (65%) compared to adolescents with good asthma control (17%) (p<0.01). The former group revealed several benefits from internet based asthma self-management: feasible electronic monitoring, easily accessible information, email communication and use of an electronic action plan. Personal benefits included the ability to react to change and to optimize asthma control. Patients with poor asthma control were able and ready to incorporate internet based asthma self-management for a long period of time (65%), whereas patients with good control were not (11%) (p<0.01). Conclusions Our findings reveal a need for support of self-management in adolescents with poorly controlled asthma that can be met by application of novel information and communication technologies. Internet based self-management should therefore target adolescents with poor asthma control.

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N Engl J Med. 2007 Mar 29;356(13):1327-37. Comment in: N Engl J Med. 2007 Mar 29;356(13):1367-9.
Asthma control during the year after bronchial thermoplasty.
Cox G, Thomson NC, Rubin AS, Niven RM, Corris PA, Siersted HC, Olivenstein R, Pavord ID, McCormack D, Chaudhuri R, Miller JD, Laviolette M; AIR Trial Study Group.
St. Joseph's Healthcare, McMaster University, Hamilton, ON, Canada. coxp@mcmaster.ca

BACKGROUND: Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma. METHODS: We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting beta2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed. RESULTS: The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16+/-0.37 vs. 0.04+/-0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3+/-48.7 vs. 8.5+/-44.2 liters per minute), scores on the AQLQ (1.3+/-1.0 vs. 0.6+/-1.1) and ACQ (reduction, 1.2+/-1.0 vs. 0.5+/-1.0), the percentage of symptom-free days (40.6+/-39.7 vs. 17.0+/-37.9), and symptom scores (reduction, 1.9+/-2.1 vs. 0.7+/-2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment. CONCLUSIONS: Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov].). Copyright 2007 Massachusetts Medical Society.

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Allergy Asthma Proc. 2007 Jan-Feb;28(1):44-9.
Allergen immunotherapy: present and future.
Finegold I.
Institute of Allergy, St. Luke's-Roosevelt Hospital, New York, New York 10022, USA. drfinegold@aol.com

In this article the present and future of immunotherapy is discussed under four general headings: (1) present understanding of mechanisms of immunotherapy, (2) present status of clinical efficacy of immunotherapy, (3) changes/challenges of immunotherapy on the horizon, and (4) future of immunotherapy. The mechanisms of immunotherapy are well delineated and show that immunotherapy alters the natural course of allergic disease. There is a reduction in inflammation, nonspecific hyperresponsiveness, prevention of new sensitivities, and progression of allergic rhinitis to asthma. Further efficacy continues after cessation of immunotherapy. Complete asthma control does not occur with pharmacotherapy. There is a need to recognize that adding treatment for asthma's allergic component with immunotherapy may be the solution to achieving the unmet goals of asthma therapy. There are new developments and challenges to the role of immunotherapy on the horizon but, at present, subcutaneous immunotherapy is the specific allergen treatment of choice in the United States.

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J Aerosol Med. 2007 Spring;20(1):1-6.
Formoterol turbuhaler is as effective as salbutamol diskus in relieving adenosine-induced bronchoconstriction in children.
Amirav I, Yacobov R, Luder AS.
Department of Paediatrics, Sieff Hospital, Safed, Israel. amirav@012.net.il

Salbutamol diskus (SD) and formoterol turbuhaler (FT) are both fast-acting beta(2) agonists delivery systems used to relieve bronchoconstriction, such as that which accompanies acute exacerbations of asthma. Although SD (which is used only on an as-needed basis) is flow independent, the FT (currently recommended for regular therapy) requires a forceful deep inspiration. Thus, the efficacy of FT in children with bronchoconstriction may be inferior to that of SD. We have studied the bronchodilatation response induced by FT after a standard adenosine-5-monophosphate (AMP) bronchial challenge, and compared it to that induced by SD, and placebo. Seventeen children (mean age +/- SD 10.3 +/- 1.7 y) with asthma underwent three AMP challenges, each time followed by inhalation of either placebo, SD (200 mug) or FT (9 mug), in random order. Patterns of bronchodilatation (forced expiratory volume in 1 second recovery) to 90% of baseline levels were compared. Both SD and FT were significantly better than placebo. FT was slightly better than SD, but this difference was not statistically significant. FT and SD are both effective bronchodilators and may be of comparable efficiency during acute bronchoconstriction in young children with asthma.

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J Allergy Clin Immunol. 2007 Jan 2; [Epub ahead of print]
Air trapping in mild and moderate asthma: Effect of inhaled corticosteroids.
Tunon-de-Lara JM, Laurent F, Giraud V, Perez T, Aguilaniu B, Meziane H, Basset-Merle A, Chanez P.
>From Universite Bordeaux 2, F-33076 Bordeaux, Institut National de la Sante et de la Recherche Medicale U885, F-33076 Bordeaux, Centre Hospitalier Universitaire (CHU) de Bordeaux, F-33076 Bordeaux, Service des Maladies Respiratoires.

BACKGROUND: Air trapping reflects small airway obstruction in asthma and can be assessed quantitatively by high-resolution computed tomography (HRCT). Hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) is deposited across all sizes of airways, including the small ones. However, its long-term effect on air trapping remains unknown in uncontrolled asthma. OBJECTIVES: To compare the effect of inhaled corticosteroids of different particle size-HFA-BDP and fluticasone propionate (FP)-on lung attenuation in mild-to-moderate uncontrolled asthma. METHODS: A randomized study was performed to analyze the effect of HFA-BDP (400 mug/d) or FP (500 mug/d) given over a period of 3 months to patients with uncontrolled mild-to-moderate asthma. HRCT was performed with spirometric gating, and lung attenuation was measured at residual volume and at pulmonary total capacity. The difference between inspiratory and expiratory attenuation was calculated as an air trapping index. RESULTS: Twenty-five out of 58 patients had abnormal air trapping and could be included in the study. Lung attenuation significantly diminished in the posterior zones of the lung after a 3-month treatment with HFA-BDP or FP, but the difference between the groups was not significant. Adjusted mean variations of the air trapping index from baseline to treatment completion were 34.3 (11.2, 57.3) and 27.3 (6.4, 48.2) for the HFA-BDP and FP groups, respectively. However, the reduction of air trapping area was more pronounced in the group treated with HFA-BDP. CONCLUSION: Inhaled corticosteroids decrease air trapping in uncontrolled asthma regardless of their particle size. CLINICAL IMPLICATIONS: In mild-to-moderate asthma, air trapping assessed by HRCT may be a new outcome related to the control of the disease.

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Dtsch Med Wochenschr. 2007 Jan;132(1/02):33-39.
[Safety of long acting beta2-agonists in the management of asthma.]
[Article in German]
Gillissen A, Berdel D, Buhl R, Criee CP, Kardos P, Magnussen H, Rabe KF, Rolke M, Vogelmeier C, Worth H, Virchow JC.
Robert Koch-Klinik, Thoraxzentrum des Klinikums St. Georg, Leipzig.

Modern drug treatment of asthma has resulted in an impressive reduction of mortality, rates of exacerbation and the frequency of emergency treatment. This effect is in particular the result of the introduction of long-term therapy with inhaled corticosteroids (ICS), which have also been shown to significantly reduce the mortality rate from asthma. By combining long-acting beta2 agonists with ICS administration the exacerbation rate can be further reduced, even when the ICS dosage is reduced. For this reason combination therapy with long-acting beta2 agonists and ICS should always be prescribed in patients with unstable asthma when on appropriately dosed ICS administration alone. The recently published SMART study (Salmeterol Multicenter Asthma Research Trial) has again revitalized a long-lasting discussion about the increased risk of severe asthma exacerbations and of asthma-related death caused by beta2 agonist therapy. In this trial there was a small but significant increase in asthma-related deaths of patients receiving salmeterol compared with patients on placebo. Based on previous reports and as a result of this recent findings, the US Food and Drug Administration (FDA) imposed a "black box" warning for the use of the long-acting beta2 agonist salmeterol, including the fixed combination of salmeterol/fluticasone, as well as of formoterol. The warning appropriately alerts doctors to findings of which they should be aware. What are the consequences for clinicians prescribing long-acting beta2 agonists? Although such long-acting agonists provide sustained bronchodilation and improve asthma control, they should only be used in adults and children with stage III asthma who have not adequately responded to other asthma controlling medications, such as low-to-medium doses of inhaled corticosteroids (ICS). They must be prescribed only in combination with ICS.

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Pediatr Emerg Care. 2006 Dec;22(12):786-93.
Single-dose oral dexamethasone in the emergency management of children with exacerbations of mild to moderate asthma.
Altamimi S, Robertson G, Jastaniah W, Davey A, Dehghani N, Chen R, Leung K, Colbourne M.
Division of Emergency Medicine, Department of Pediatrics, University of British Columbia and British Columbia's Children's Hospital, Vancouver, B.C., Canada.

OBJECTIVE: To compare the efficacy of a single dose of oral dexamethasone (Dex) versus 5 days of twice-daily prednisolone (Pred) in the management of mild to moderate asthma exacerbations in children. STUDY DESIGN: A prospective, randomized, double-blinded trial of children 2 to 16 years of age who presented to the emergency department (ED) with acute mild to moderate asthma exacerbations. Subjects received single-dose oral Dex (0.6 mg/kg to a maximum of 18 mg) or oral Pred (1 mg/kg per dose to a maximum of 30 mg) twice daily for 5 days. After discharge, subjects were contacted by telephone at 48 h to assess symptoms and reevaluated in the ED in 5 days. The primary outcome was the number of days needed for Patient Self Assessment Score to return to baseline (score of 0-0.5). MAIN RESULTS: Baseline characteristics of the 2 groups were similar. The mean number of days needed for Patient Self Assessment Score to return to baseline (0-0.5) in the Dex and Pred groups were 5.21 versus 5.22 days, respectively (mean difference, -0.01; confidence interval, -0.70, 0.68). Pulmonary index scores were similar in both groups at initial presentation, initial ED discharge and at the day 5 follow-up visit. At the first visit, mean time to discharge was 3.5 h (+/-1.93)for Dex and 4.3 h (+/-3.67) for Pred (mean difference, -0.8; confidence interval, -1.8, 0.2). Initial admission rate was 9% (Dex) versus 13.4% (Pred). There was no significant difference in the number of salbutamol therapies needed in the ED nor at home after discharge. For subjects discharged home, the admission rate after initial discharge was 4.9% (Dex) versus 1.8% (Pred), resulting in overall hospital admission rates of 13.4% (Dex) and 14.9% (Pred). CONCLUSION: A single dose of oral Dex (0.6 mg/kg) is no worse than 5 days of twice-daily prednisolone (1 mg/kg per dose) in the management of children with mild to moderate asthma.

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Neth J Med. 2006 Dec;64(11):417-21.
The safety of electroconvulsive therapy in patients with asthma.
Mueller PS, Schak KM, Barnes RD, Rasmussen KG.
Divisions of General Internal Medicine, Tertiary Psychiatry and Psychology, and Cardiovascular and Thoracic Anaesthesia, Mayo Clinic, Rochester, Minnesota, USA.

Background: Patients with depression and other psychiatric disorders being considered for electroconvulsive therapy (ECT) may also have asthma. Since ECT requires the administration of general anaesthesia, it is assumed that extra care should be taken with asthmatic patients before and during ECT. We sought to investigate the safety of ECT in asthmatic patients. Methods: A retrospective review was conducted of the medical records of all of the patients with currently active and managed asthma who underwent ECT for severe depressive syndromes at Mayo Clinic, Rochester, Minnesota, between 1 January 1998, and 30 June 2006. Results: Thirty-four patients with asthma who also underwent ECT were identified. Of these, 27 (79%) were women. The median age was 45 years (range 23-84 years). All 34 patients were using asthma medications daily at the time of ECT. The 34 patients underwent a total of 459 ECT sessions. Four (12%) patients experienced exacerbation of their asthma on a total of five occasions. Each exacerbation was successfully treated with standard asthma medications, and all four patients completed their courses of ECT. Conclusion: ECT in patients with asthma appears to be safe. Although exacerbation of asthma after ECT was rare in our series, a prospective study would be needed to determine the precise risk of pulmonary omplications of ECT in asthmatic patients.

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J Asthma. 2006 Dec;43(10):765-72.
The Efficacy and Safety of Mometasone Furoate Delivered via a Dry Powder Inhaler for the Treatment of Asthma.
Meltzer EO, Wenzel S.
Allergy and Asthma Medical Group and Research Center, University of California, San Diego, California, USA.

Inhaled corticosteroids are the gold standard of daily therapy for effective control of all stages of persistent asthma. For this review of the new inhaled corticosteroid mometasone furoate, a MEDLINE/PubMed search using the terms "mometasone furoate AND asthma" found 57 articles, 17 of which presented data from efficacy and safety studies reviewed herein. In clinical trials, once-daily evening dosing of mometasone furoate delivered via dry powder inhaler (200 or 400 mu g/day) was effective in patients with mild to moderate asthma previously treated with short-acting beta2-agonists alone and in those previously maintained on inhaled corticosteroid therapy. In patients with severe asthma, mometasone furoate 400 mu g twice daily eliminated or reduced the need for oral prednisone while improving lung function, asthma symptoms, and quality of life. Clinical studies have shown that mometasone furoate is generally well tolerated and has minimal systemic activity at recommended doses. In conclusion, mometasone furoate provides primary care and specialty physicians with a safe, effective, and convenient option to meet the challenges of asthma management.

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Crit Care. 2006 Dec 20;10(6):241 [Epub ahead of print]
Clinical review: Use of helium-oxygen in critically ill patients.
Gainnier M, Forel JM.
Service de Reanimation Medicale, CHU de Marseille, Hopital Sainte Marguerite, Bd de Sainte Marguerite, 13274 Marseille Cedex 9, France,. marc.gainnier@ap-hm.fr.

ABSTRACT: Use of helium-oxygen (He/O2) mixtures in critically ill patients is supported by a reliable and well understood theoretical rationale and by numerous experimental observations. Breathing He/O2 can benefit critically ill patients with severe respiratory compromise mainly by reducing airway resistance in obstructive syndromes such as acute asthma and decompensated chronic obstructive pulmonary disease. However, the benefit from He/O2 in terms of respiratory mechanics diminishes rapidly with increasing oxygen concentration in the gaseous mixture. Safe use of He/O2 in the intensive care unit requires specific equipment and supervision by adequately experienced personnel. The available clinical data on inhaled He/O2 mixtures are insufficient to prove that this therapy has benefit with respect to outcome variables. For these reasons, He/O2 is not currently a standard of care in critically ill patients with acute obstructive syndromes, apart from in some, well defined situations. Its role in critically ill patients must be more precisely defined if we are to identify those patients who could benefit from this therapeutic approach.
 

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