In 1997, the National Asthma Education and Prevention Program (NAEPP), coordinated by the National Heart, Lung, and Blood Institute, published the second Expert Panel Report (EPR-2): Guidelines for the Diagnosis and Management of Asthma (National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the diagnosis and management of asthma. Bethesda MD.: US Department of Health and Human Services, National Institutes of Health, 1997; publication no. 97-4051. Available at http://www.nhlbi.nih.gov.ezproxy.puc.cl/guidelines/asthma/asthgdln.pdf). Subsequently, the NAEPP Expert Panel identified key questions regarding asthma management that were submitted to an evidence practice center of the Agency for Healthcare Research and Quality to conduct a systematic review of the evidence. The resulting evidence report was used by the Expert Panel to update recommendations for clinical practice on selected topics. These recommendations (EPR-Update 2002) were published in 2002. (National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma -- update on selected topics 2002. J Allergy Clin Immunol 2002;110[November 2002, part 2]. Available at http://www.nhlbi.nih.gov.ezproxy.puc.cl/guidelines/asthma/index.htm).

PURPOSE OF REVIEW:

This review examines the commencement of maintenance pharmacotherapy for asthma: inhaled corticosteroids alone or in combination with long-acting β2 agonists.

RECENT FINDINGS:

A systematic review of randomized controlled trials has examined the starting dose of inhaled corticosteroids (high, moderate, low) and the dose regimen (step down versus constant) in asthma. There was no significant difference in key asthma outcomes for step down compared with a constant inhaled corticosteroid dose. There was no significant difference between high or moderate dose inhaled corticosteroid groups (n = 11) for morning peak expiratory flow, symptoms and rescue medication use. There may be a benefit from high-dose inhaled corticosteroids for airway hyperresponsiveness. There was a significant improvement in peak expiratory flow and nocturnal symptoms in favour of a moderate inhaled corticosteroid dose compared with low-dose treatment. Long-acting β2 agonists combined with inhaled corticosteroids as initial asthma therapy has been examined in a systematic review of nine randomized controlled trials. Inhaled corticosteroids combined with long-acting β2 agonists led to significant improvements in forced expiratory volume in 1 s, morning peak expiratory flow, symptom score and symptom-free days but no difference in exacerbations requiring oral corticosteroids. A randomized controlled trial of patients with uncontrolled asthma found a benefit of escalating doses of salmeterol/fluticasone compared with fluticasone on asthma control.

SUMMARY:

Initial inhaled corticosteroid therapy should begin with a constant, moderate dose. Initial therapy with long-acting β2 agonist and inhaled corticosteroids achieves superior improvement in symptoms and lung function, and at a quicker rate than inhaled corticosteroids alone. There is no benefit in terms of reduced exacerbations unless an escalating inhaled corticosteroid dose strategy is used. © 2006 Lippincott Williams & Wilkins.

BACKGROUND:

In some people with asthma, expiratory airflow limitation, premature closure of small airways, activity of inspiratory muscles at the end of expiration and reduced pulmonary compliance may lead to lung hyperinflation. With the increase in lung volume, chest wall geometry is modified, shortening the inspiratory muscles and leaving them at a sub-optimal position in their length-tension relationship. Thus, the capacity of these muscles to generate tension is reduced. An increase in cross-sectional area of the inspiratory muscles caused by hypertrophy could offset the functional weakening induced by hyperinflation. Previous studies have shown that inspiratory muscle training promotes diaphragm hypertrophy in healthy people and patients with chronic heart failure, and increases the proportion of type I fibres and the size of type II fibres of the external intercostal muscles in patients with chronic obstructive pulmonary disease. However, its effects on clinical outcomes in patients with asthma are unclear.

OBJECTIVES:

To evaluate the efficacy of inspiratory muscle training with either an external resistive device or threshold loading in people with asthma.

SEARCH METHODS:

We searched the Cochrane Airways Group Specialised Register of trials, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and reference lists of included studies. The latest search was performed in November 2012.

SELECTION CRITERIA:

We included randomised controlled trials that involved the use of an external inspiratory muscle training device versus a control (sham or no inspiratory training device) in people with stable asthma.

DATA COLLECTION AND ANALYSIS:

We used standard methodological procedures expected by The Cochrane Collaboration.

MAIN RESULTS:

We included five studies involving 113 adults. Participants in four studies had mild to moderate asthma and the fifth study included participants independent of their asthma severity. There were substantial differences between the studies, including the training protocol, duration of training sessions (10 to 30 minutes) and duration of the intervention (3 to 25 weeks). Three clinical trials were produced by the same research group. Risk of bias in the included studies was difficult to ascertain accurately due to poor reporting of methods.
The included studies showed a statistically significant increase in inspiratory muscle strength, measured by maximal inspiratory pressure (PImax) (mean difference (MD) 13.34 cmH2O, 95% CI 4.70 to 21.98, 4 studies, 84 participants, low quality evidence). Our other primary outcome, exacerbations requiring a course of oral or inhaled corticosteroids or emergency department visits, was not reported. For the secondary outcomes, results from one trial showed no statistically significant difference between the inspiratory muscle training group and the control group for maximal expiratory pressure, peak expiratory flow rate, forced expiratory volume in one second, forced vital capacity, sensation of dyspnoea and use of beta2-agonist. There were no studies describing inspiratory muscle endurance, hospital admissions or days off work or school.

AUTHORS' CONCLUSIONS:

There is no conclusive evidence in this review to support or refute inspiratory muscle training for asthma. The evidence was limited by the small number of trials with few participants together with the risk of bias. More well conducted randomised controlled trials are needed. Future trials should investigate the following outcomes: lung function, exacerbation rate, asthma symptoms, hospital admissions, use of medications and days off work or school. Inspiratory muscle training should also be assessed in people with more severe asthma and conducted in children with asthma.

ANTECEDENTES:

La inmunoterapia específica con alergenos ha sido, durante mucho tiempo, un tratamiento polémico para el asma. Aunque los efectos beneficiosos sobre las medidas de resultado clínicamente pertinentes se han demostrado en los ensayos controlados con asignación aleatoria, prevalece el riesgo anafilaxia grave y a veces mortal. Las recomendaciones de los organismos profesionales varían de la aceptación cautelosa al rechazo rotundo. Dado el creciente interés en las nuevas preparaciones de alergenos y en los métodos de administración nuevos, actualizamos la revisión sistemática de inmunoterapia específica con alergenos para el asma.

OBJETIVOS:

El objetivo de esta revisión fue evaluar los efectos de la inmunoterapia específica con alergenos para el asma.

ESTRATEGIA DE BÚSQUEDA:

Se hicieron búsquedas en el Registro Especializado de Ensayos Controlados del Grupo Cochrane de Vías Respiratorias (Cochrane Airways Group) Trials Register hasta 2005, Dissertation Abstracts y en Current Contents.

CRITERIOS DE SELECCIÓN:

Los ensayos controlados con asignación aleatoria que utilizan diversas formas de inmunoterapia específica con alergenos para tratar el asma y que informan, al menos, una medida de resultado clínica.

OBTENCIÓN Y ANÁLISIS DE LOS DATOS:

Tres autores evaluaron de forma independiente la admisibilidad de los estudios para su inclusión. Dos autores, de forma independiente, realizaron la evaluación de la calidad de los estudios.

RESULTADOS PRINCIPALES:

Se incluyeron 88 ensayos (13 nuevos ensayos). Había 42 ensayos sobre inmunoterapia para la alergia al ácaro doméstico; 27 ensayos sobre alergia al polen; 10 ensayos sobre alergia a la caspa animal; dos sobre la alergia al moho Cladosporium, dos al látex y seis ensayos que estudiaron alergenos múltiples. La ocultación de la asignación se evaluó como claramente adecuada en sólo 16 de los ensayos. La heterogeneidad significativa estaba presente en varias comparaciones. En general, se observó una reducción significativa de los síntomas de asma y de la medicación, como también mejoría en la hiperreactividad bronquial después de la inmunoterapia.Se observó una mejoría significativa en las puntuaciones de síntomas de asma (diferencia de medias estandarizada −0,59; intervalo de confianza del 95%: −0,83 a −0,35) y hubiera sido necesario tratar tres pacientes (IC del 95%: 3 a 5) con inmunoterapia para evitar el deterioro de los síntomas de asma en uno de ellos.En general, hubiera sido necesario tratar cuatro pacientes (IC del 95%: 3 a 6) con inmunoterapia para evitar que uno necesitara más medicación. La inmunoterapia con alergenos redujo de forma significativa la hiperreactividad bronquial específica al alergeno, junto a alguna reducción de hiperreactividad bronquial no específica. No se observó ningún efecto consistente en la función pulmonar. Si 16 pacientes fueran tratados con inmunoterapia, se esperaría que uno desarrollara una reacción adversa local.Si nueve pacientes fueran tratados con inmunoterapia, se esperaría que uno desarrollara una reacción sistémica (de cualquier gravedad).

CONCLUSIONES DE LOS AUTORES:

La inmunoterapia reduce los síntomas y el uso de los medicamentos para el asma y mejora la hiperreactividad bronquial. Un ensayo encontró que es posible comparar el tamaño del beneficio al de los esteroides inhalados. Debe considerarse la posibilidad de efectos adversos locales o sistémicos (como anafilaxia).

BACKGROUND:

Asthma is a chronic disease of inflammation and smooth muscle dysfunction, including bronchoconstriction. These symptoms are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. Psychological factors may influence the symptoms and management of asthma in children in many ways, for example, evidence suggests that emotional stress can either precipitate or exacerbate both acute and chronic asthma.

OBJECTIVES:

To assess the efficacy of psychological interventions in improving health and behavioural outcomes for children with asthma.

SEARCH METHODS:

The Cochrane Airways Group Specialised Register and PsycINFO were searched with pre-defined terms up until April 2007.

SELECTION CRITERIA:

Randomised controlled trials published in any language assessing the effects of a psychological intervention compared with a control intervention in children and adolescents with asthma were included in the review. Cross-over trials were considered inappropriate for studies using psychological interventions and were therefore excluded from this systematic review.

DATA COLLECTION AND ANALYSIS:

Two reviewers assessed the relevance of abstracts identified by electronic searching and retrieved agreed studies for further scrutiny. The studies that met the inclusion criteria were assembled and data extracted.

MAIN RESULTS:

Twelve studies (588 children) were included in the review. Study quality was poor and sample sizes were frequently small. A meta-analysis was possible on two studies only examining the effects of relaxation therapy on PEFR which favoured the treatment group (32 L/min, 95% CI 13 to 50 L/min). No other meta-analysis could be performed due to the diversity of interventions and the outcomes assessed. In addition, many studies reported insufficient data.

AUTHORS' CONCLUSIONS:

This review was unable to draw firm conclusions for the role of psychological interventions for children with asthma. This review demonstrates the absence of an adequate evidence base and highlights the need for well-conducted and reported randomised trials in this area.

BACKGROUND:

'The Alexander technique' is a taught form of physical therapy involving a series of movements designed to correct posture and bring the body into natural alignment with the object of helping it to function efficiently, and is reported to aid relaxation. Some practitioners claim benefits for those who desire greater ease and efficiency of breathing, including asthmatics.

OBJECTIVES:

The objective of this review was to evaluate the efficacy of the Alexander technique in people with chronic, stable asthma.

SEARCH METHODS:

We searched the Cochrane Airways Group Specialised Register, the Cochrane Complementary Medicine Field trials register and the bibliographies of relevant articles. The most recent search was run in June 2012.

SELECTION CRITERIA:

Randomised controlled trials of Alexander technique (AT) for the improvement of the symptoms of chronic, stable asthma, comparing the treatment with either another intervention or no intervention.

DATA COLLECTION AND ANALYSIS:

No trials were found that met the selection criteria.

MAIN RESULTS:

No meta-analysis could be performed.

AUTHORS' CONCLUSIONS:

Robust, well-designed randomised controlled trials are required in order to test claims by practitioners that AT can have a positive effect on the symptoms of chronic asthma and thereby help people with asthma to reduce medication.

Introduction: The objective of this paper is to systematically review the existing evidence of the effectiveness and safety profile of a long-acting inhaled muscarinic antagonist as add-on therapy in patients with asthma that is uncontrolled despite inhaled corticosteroid (ICS) use. Methods: With the assistance of two experienced research librarians, we searched Ovid MEDLINE/PubMed (1946 to September 12, 2013), the Cochrane Library review, and the TRIP database. The key search terms were "tiotropium and asthma." The search was limited to human data published in English. Included in the systematic review were all randomized controlled trials that evaluated the efficacy of tiotropium in patients with asthma. The clinical trials had to be at least 4 weeks in duration and to provide adequate information on clinically appropriate end points in asthma care (eg, change in lung function, exacerbation rates, and/or ICS dosing). Data on patient characteristics, study design, outcome measures, concomitant asthma medication, and adverse events were extracted from the full text of each included individual study. Marked heterogeneity of study design precluded statistical pooling of results for a meta-analysis. Consequently, only descriptive summaries of outcomes are provided. Results: Our database search retrieved 149 citations. We found five randomized controlled trials in humans that met our criteria for inclusion in the systematic review. We also found two open-label uncontrolled trials that were considered in the discussion. Each of the five included studies met the Consolidated Standards of Reporting Trials criteria for a well-designed randomized trial. Discussion: The five clinical studies included in this systematic review focused on evaluating the efficacy of tiotropium as add-on therapy to ICS or ICS in combination with a long-acting inhaled β2-agonist (LABA) in patients with uncontrolled moderate to severe persistent asthma. Tiotropium maintained lung function when ICSs were tapered and when an LABA was discontinued. Tiotropium improved lung function when added to ICS alone or ICS-LABA combination therapy. In the only trial to have compared the addition of tiotropium with doubling the dose of ICS, tiotropium provided significantly superior results. In trials in which the addition of tiotropium was compared with salmeterol, the beneficial effects of these two bronchodilators were similar. No safety concerns were found with use of tiotropium as add-on therapy. Conclusion: Tiotropium may have a beneficial role in moderate to severe persistent asthma despite use of an ICS or ICS and LABA. Use of tiotropium as add-on therapy poses no safety concerns. © 2014 Befekadu et al.

Background: Asthma is a respiratory (airway) condition that affects an estimated 300 million people worldwide and is associated with significant morbidity and mortality. Omalizumab is a monoclonal antibody that binds and inhibits free serum immunoglobulin E (IgE). It is called an 'anti-IgE' drug. IgE is an immune mediator involved in clinical manifestations of asthma. A recent update of National Institute for Health and Care Excellence (NICE) guidance in 2013 recommends omalizumab for use as add-on therapy in adults and children over six years of age with inadequately controlled severe persistent allergic IgE-mediated asthma who require continuous or frequent treatment with oral corticosteroids. Objectives: To assess the effects of omalizumab versus placebo or conventional therapy for asthma in adults and children. Search methods: We searched the Cochrane Airways Group Specialised Register of trials for potentially relevant studies. The most recent search was performed in June 2013. We also checked the reference lists of included trials and searched online trial registries and drug company websites. Selection criteria: Randomised controlled trials examining anti-IgE administered in any manner for any duration. Trials with co-interventions were included, as long as they were the same in each arm. Data collection and analysis: Two review authors independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature: inhaled, intravenous and subcutaneous injection. The main focus of the updated review is subcutaneous administration, as this route is currently used in clinical practice. Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources. Main results: In all, 25 trials were included in the review, including 11 new studies since the last update, for a total of 19 that considered the efficacy of subcutaneous anti-IgE treatment as an adjunct to treatment with corticosteroids. For participants with moderate or severe asthma who were receiving background inhaled corticosteroid steroid (ICS) therapy, a significant advantage favoured subcutaneous omalizumab with regard to experiencing an asthma exacerbation (odds ratio (OR) 0.55, 95% confidence interval (CI) 0.42 to 0.60; ten studies, 3261 participants). This represents an absolute reduction from 26% for participants suffering an exacerbation on placebo to 16% on omalizumab, over 16 to 60 weeks. A significant benefit was noted for subcutaneous omalizumab versus placebo with regard to reducing hospitalisations (OR 0.16, 95% CI 0.06 to 0.42; four studies, 1824 participants), representing an absolute reduction in risk from 3% with placebo to 0.5% with omalizumab over 28 to 60 weeks. No separate data on hospitalisations were available for the severe asthma subgroup, and all of these data were reported for participants with the diagnosis of moderate to severe asthma. Participants treated with subcutaneous omalizumab were also significantly more likely to be able to withdraw their ICS completely than those treated with placebo (OR 2.50, 95% CI 2.00 to 3.13), and a small but statistically significant reduction in daily inhaled steroid dose was reported for omalizumab-treated participants compared with those given placebo (weighted mean difference (WMD) -118 mcg beclomethasone dipropionate (BDP) equivalent per day, 95% CI -154 to -84). However, no significant difference between omalizumab and placebo treatment groups was seen in the number of participants who were able to withdraw from oral corticosteroid (OCS) therapy (OR 1.18, 95% CI 0.53 to 2.63). Participants treated with subcutaneous omalizumab as an adjunct to treatment with corticosteroids required a small but significant reduction in rescue beta2-agonist medication compared with placebo (mean difference (MD) -0.39 puffs per day, 95% CI -0.55 to -0.24; nine studies, 3524 participants). This benefit was observed in both the moderate to severe (MD -0.58, 95% CI -0.84 to -0.31) and severe (MD -0.30, 95% CI -0.49 to -0.10) asthma subgroups on a background therapy of inhaled corticosteroids; however, no significant difference between subcutaneous omalizumab and placebo was noted for this outcome in participants with severe asthma who were receiving a background therapy of inhaled plus oral corticosteroids. Significantly fewer serious adverse events were reported in participants assigned to subcutaneous omalizumab than in those receiving placebo (OR 0.72, 95% CI 0.57 to 0.91; 15 studies, 5713 participants), but more injection site reactions were observed (from 5.6% with placebo to 9.1% with omalizumab). To reflect current clinical practice, discussion of the results is limited to subcutaneous use, and trials involving intravenous and inhaled routes have been archived. Authors' conclusions: Omalizumab was effective in reducing asthma exacerbations and hospitalisations as an adjunctive therapy to inhaled steroids and during steroid tapering phases of clinical trials. Omalizumab was significantly more effective than placebo in increasing the numbers of participants who were able to reduce or withdraw their inhaled steroids. Omalizumab was generally well tolerated, although more injection site reactions were seen with omalizumab. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS. Although subgroup analyses suggest that participants receiving prednisolone had better asthma control when they received omalizumab, it remains to be tested prospectively whether the addition of omalizumab has a prednisolone-sparing effect. It is also not clear whether there is a threshold level of baseline serum IgE for optimum efficacy of omalizumab. Given the high cost of the drug, identification of biomarkers predictive of response is of major importance for future research. © 2014 The Cochrane Collaboration.

BACKGROUND:

The Childhood Asthma Management Program, a 5-year randomized clinical trial of treatments for childhood asthma, has enrolled and characterized a cohort of 1041 children with mild-to-moderate asthma.

OBJECTIVE:

We sought to describe self-reported sensitivities and environmental exposures and investigate the relationships between self-report of these exposures as asthma triggers and their prevalence in the home.

METHODS:

Self-reports of sensitivities and home exposures were obtained by interview with the child or parent. Sensitivities were further assessed by using allergy skin testing (prick or puncture) against a core battery of allergens. Home exposures were further assessed by using analysis of a home dust sample.

RESULTS:

Environmental exposures were surprisingly common despite self-reported sensitivities to environmental factors. Of patients reporting that cigarette smoking frequently causes asthma symptoms, 26% reported having at least one parent who smokes cigarettes. Thirty-nine percent of patients reporting that exposure to animals frequently causes asthma symptoms live with a furry pet in their home. We found a smaller proportion of homes with a high level of cat allergen (P <.001) among the children who reported that animals frequently or always trigger asthma symptoms compared with those who reported that animals never or occasionally trigger asthma symptoms, suggesting modification of the home environment. No such results were seen for dog exposure. However, clinical symptoms did not reduce exposure to parental cigarette smoking (P =.15), house dust (P =.31), or damp and musty areas (P =.51).

CONCLUSION:

These data suggest that children with mild-to-moderate asthma are frequently symptomatic and exposed to a wide variety of environmental exposures that are perceived to trigger symptoms by means of self-report. Although environmental modification of asthmatic homes may occur, many children remain exposed to agents that are known to trigger their asthma.

OBJECTIVE:

This study was undertaken to educate physicians on the safety of asthma controller use during pregnancy.

STUDY DESIGN:

A comprehensive literature search using MEDLINE, the Cochrane Controlled Trials Register and Database of Systematic Reviews, EMBASE, and selected bibliographies identified human gestational studies of asthma controller medications from which maternal and fetal outcomes were obtained. The US Food and Drug Administration (FDA) pregnancy category ratings were identified from product package inserts.

RESULTS:

Human gestational studies were identified for the inhaled corticosteroids (ICSs) beclomethasone, budesonide, and triamcinolone and for cromolyn sodium, theophylline, and salmeterol. Human pregnancy data support an FDA Pregnancy Category B rating for budesonide. Pregnancy Category B ratings for cromolyn, nedocromil, montelukast, and zafirlukast are based primarily on safety in animal reproduction studies. ICSs other than budesonide, theophylline, zileuton, and long-acting beta 2 -adrenergic agonists are Pregnancy Category C.

CONCLUSION:

Human pregnancy data for many asthma controllers are lacking; nonetheless, data support a range of choices among medications rated Pregnancy Category B.