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.

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.

BACKGROUND:

Telehealthcare has the potential to provide care for long-term conditions that are increasingly prevalent, such as asthma. We conducted a systematic review of studies of telehealthcare interventions used for the treatment of asthma to determine whether such approaches to care are effective.

METHODS:

We searched the Cochrane Airways Group Specialised Register of Trials, which is derived from systematic searches of bibliographic databases including CENTRAL (the Cochrane Central Register of Controlled Trials), MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and PsycINFO, as well as other electronic resources. We also searched registers of ongoing and unpublished trials. We were interested in studies that measured the following outcomes: quality of life, number of visits to the emergency department and number of admissions to hospital. Two reviewers identified studies for inclusion in our meta-analysis. We extracted data and used fixedeffect modelling for the meta-analyses.

RESULTS:

We identified 21 randomized controlled trials for inclusion in our analysis. The methods of telehealthcare intervention these studies investigated were the telephone and video- and Internet-based models of care. Meta-analysis did not show a clinically important improvement in patients' quality of life, and there was no significant change in the number of visits to the emergency department over 12 months. There was a significant reduction in the number of patients admitted to hospital once or more over 12 months (risk ratio 0.25 [95% confidence interval 0.09 to 0.66]).

INTERPRETATION:

We found no evidence of a clinically important impact on patients' quality of life, but telehealthcare interventions do appear to have the potential to reduce the risk of admission to hospital, particularly for patients with severe asthma. Further research is required to clarify the cost-effectiveness of models of care based on telehealthcare.

OBJECTIVE:

To measure the effect of an asthma intervention on the functional status and morbidity of children with undiagnosed asthma.

STUDY DESIGN:

Data from a randomized trial were used to compare outcomes at baseline and follow-up for children with undiagnosed and diagnosed asthma. We studied 510 symptomatic children with diagnosed asthma (diagnosed) and 299 children with symptoms but no diagnosis (undiagnosed). Baseline functioning and morbidity were similar for undiagnosed and diagnosed patients classified as moderate-severe.

RESULTS:

There were fewer undiagnosed reported allergies, seasonal symptoms, and other respiratory diagnoses (all P < 0.01). Among the moderate-severe, functional status, for example, symptom-days ( P = .02), symptom-nights ( P < .01), and days of restricted activity ( P < .01), was significantly reduced at follow-up for the undiagnosed in the intervention group but not for undiagnosed control subjects. Findings were similar for children with diagnosed asthma.

CONCLUSIONS:

Children with undiagnosed asthma were generally nonatopic, although some had symptoms at a level comparable to children with a diagnosis. The intervention successfully improved functional status for children with undiagnosed asthma as well as for children with diagnosed asthma. These results can be applied to ongoing discussions related to case detection.

Background: Vilanterol (VI) is a long-acting beta2-agonist (LABA) that binds to the beta2-adrenoceptor on the airway smooth muscle, producing bronchodilation. LABA therapy, which is well established in adults as part of the British Thoracic Society (BTS) Guidelines for the Management of Asthma, leads to improvement in symptoms and lung function and reduction in exacerbations. At present, the commonly used LABAs licensed for use in asthma management (formoterol and salmeterol) require twice-daily administration, whereas VI is a once-daily therapy. Fluticasone furoate (FF) is an inhaled corticosteroid (ICS), and ICS therapy is recommended by the BTS asthma guidelines. ICSs, the mainstay of asthma treatment, lead to a reduction in both airway inflammation and airway hyper-responsiveness. Regular use leads to improvement in symptoms and lung function. ICSs are currently recommended as 'preventer' therapy for patients who use a 'reliever' medication (e.g. short-acting beta2 agonist (SABA), salbutamol) three or more times per week. Most of the commonly used ICS treatments are twice-daily medications, although two once-daily products are currently licensed (ciclesonide and mometasone). At the present time, only one once-daily ICS/LABA combination (FF/VI) is available, and several other combination inhalers are recommended for twice-daily administration. Objectives: To compare effects of VI and FF in combination versus placebo, or versus other ICSs and/or LABAs, on acute exacerbations and on health-related quality of life (HRQoL) in adults and children with chronic asthma. Search methods: We searched the Cochrane Airways Group Register of trials, clinical trial registries, manufacturers' websites and reference lists of included studies up to June 2016. Selection criteria: We included randomised controlled trials (RCTs) of adults and children with a diagnosis of asthma. Included studies compared VI and FF combined versus placebo, or versus other ICSs and/or LABAs. Our primary outcomes were health-related quality of life, severe asthma exacerbation, as defined by hospital admissions or treatment with a course of oral corticosteroids, and serious adverse events. Data collection and analysis: Two review authors independently extracted data and analysed outcomes using a fixed-effect model. We used standard Cochrane methods. Main results: We identified 14 studies that met our inclusion criteria, with a total of 6641 randomised participants, of whom 5638 completed the study. All studies lasted between two and 78 weeks and showed good methodological quality overall. We included 10 comparisons in this review, seven for which the dose of VI and FF was 100/25 mcg (VI/FF 100/25 mcg vs placebo; VI/FF 100/25 mcg vs same dose of FF; VI/FF 100/25 mcg vs same dose of VI; VI/FF 100/25 mcg vs fluticasone propionate (FP) 500 mcg twice-daily; VI/FF 100/25 mcg vs fluticasone propionate/salmeterol (FP/SAL) 250/50 mcg twice-daily; VI/FF 100/25 mcg vs FP/SAL 250/25 mcg twice-daily; FF/VI 100/25 vs FP/SAL500/50) and three for which the dose of VI and FF was 200/25 mcg (VI/FF 200/25 mcg vs placebo; VI/FF 200/25 mcg vs FP 500 mcg; VI/FF 200/25 mcg vs same dose of FF). We found very few opportunities to combine results from the 14 included studies in meta-analyses. We tabulated the data for our pre-specified primary outcomes. In particular, we found insufficient information to assess whether once-daily VI/FF was better or worse than twice-daily FP/SAL in terms of efficacy or safety. Only one of the 14 studies looked at health-related quality of life when comparing VI and FF 100/25 mcg versus placebo and identified a significant advantage of VI/FF 100/25 mcg (mean difference (MD) 0.30, 95% confidence interval (CI) 0.14 to 0.46; 329 participants); we recognised this as moderate-quality evidence. Only two studies compared VI/FF 100/25 mcg versus placebo with respect to exacerbations; both studies reported no exacerbations in either treatment arm. Five studies (VI/FF 100/25 mcg vs placebo) sought information on serious adverse events; all five studies reported no serious adverse events in the VI/FF 100/25 mcg or placebo arms. We found no comparison relevant to our primary outcomes for VI/FF at a higher dose (200/25 mcg) versus placebo. The small number of studies contributing to each comparison precludes the opportunity to draw robust conclusions for clinical practice. These studies were not of sufficient duration to allow conclusions about long-term side effects. Authors' conclusions: Some evidence suggests clear advantages for VI/FF, in combination, compared with placebo, particularly for forced expiratory volume in one second (FEV1) and peak expiratory flow; however, the variety of questions addressed in the included studies did not allow review authors to draw firm conclusions. Information was insufficient for assessment of whether once-daily VI/FF was better or worse than twice-daily FP/SAL in terms of efficacy or safety. It is clear that more research is required to reduce the uncertainties that surround interpretation of these studies. It will be necessary for these findings to be replicated in other work before more robust conclusions are revealed. Only five of the 13 included studies provided data on health-related quality of life, and only six recorded asthma exacerbations. Only one study focused on paediatric patients, so no conclusions can be drawn for the paediatric population. More research is needed, particularly in the primary outcome areas selected for this review, so that we can draw firmer conclusions in the next update of this review.

OBJECTIVE:

To provide a brief overview of the current state of evidence for chiropractic care, specifically in the management of asthma and to a lesser extent allergy.

DATA SOURCES:

A search of MEDLINE for English-language articles published between January 1966 and July 2002 was conducted using the keywords asthma, allergy, manual therapy, physical therapy techniques, chiropractic, physical therapy (specialty), physiotherapy, massage, and massage therapy. A hand search of the primary chiropractic and osteopathic literature on the treatment of asthma was performed, and proceedings from a recent research symposium on spinal manipulation were included.

STUDY SELECTION:

Clinical controlled studies and systematic reviews on spinal manipulative therapy (SMT) and asthma were selected. There were no primary clinical trials on SMT and allergy found.

RESULTS:

Many of the claims of chiropractic success in asthma have been primarily based on anecdotal evidence or uncontrolled case studies. Three recently reported randomized controlled studies showed benefit in subjective measures, such as quality of life, symptoms, and bronchodilator use; however, the differences were not statistically significant between controls and treated groups. There were no significant changes in any objective lung function measures. The clinical issues emanating from these trials are discussed.

CONCLUSIONS:

There is currently no evidence to support the use of chiropractic SMT as a primary treatment for asthma or allergy. Based on reported subjective improvement in patients receiving chiropractic care, certain clinical circumstances may warrant a therapeutic trial in patients with asthma. Further properly designed, collaborative research is needed to determine if there is a role for chiropractic SMT in the care of asthma or allergy.