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Efficacy of anti-interleukin-5 therapy with mepolizumab in patients with asthma: a meta-analysis of randomized placebo-controlled trials.

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Interleukin (IL)-5 is believed to be a key cytokine in eosinophil inflammatory infiltration in asthma. Previous clinical trials have evaluated the efficacy and safety of mepolizumab, a monoclonal antibody against IL-5, in patients with asthma. However, most of these studies were small, the conclusions were inconsistent, and the precise effects are therefore debatable.

METHODS: A meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of intravenous infusion of mepolizumab on clinical outcomes in patients with asthma. Trials were searched in PubMed, Embase, Web of Science, Cochrane CENTRAL, Scopus, reviews, and reference lists of relevant articles. The outcome variables analyzed included eosinophil counts in blood and sputum, airways outcome measures, exacerbations, asthma control, and quality of life scores.

RESULTS: Seven studies met final inclusion criteria (total n = 1131). From the pooled analyses, mepolizumab significantly reduced eosinophils in blood (MD -0.29×10(9)/L, 95% CI -0.44 to -0.14×10(9)/L, P = 0.0001) and sputum (MD -6.05%, 95% CI -9.34 to -2.77%, P = 0.0003). Mepolizumab was also associated with significantly decreased exacerbation risk than placebo (OR 0.30, 95%CI 0.13 to 0.67, P = 0.004), and with a significant improvement in the scores on the Asthma Quality of Life Questionnaire (AQLQ) (MD 0.26, 95% CI 0.03 to 0.49, P = 0.03) in patients with eosinophilic asthma. There were no statistical differences between the groups with respect to FEV1, PEF, or histamine PC20 (all P>0.05), and a non-significant trend for improvement in scores on the Juniper Asthma Control Questionnaire (JACQ) (MD -0.21, 95% CI -0.43 to 0.01, P = 0.06) in the mepolizumab group was observed.

CONCLUSIONS: Mepolizumab reduces the risk of exacerbations and improves quality of life in patients with eosinophilic asthma, but no significant improvement in lung function outcomes was observed. Further research is required to establish the possible role of anti-IL-5 as a therapy for asthma.

Airway disease in alpha-1 antitrypsin deficiency.

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Although less well appreciated than pulmonary emphysema, inflammation of the airways is an early and important finding in alpha-1 antitrypsin deficiency (AATD). The spectrum of clinical presentations of airways disease includes cough and wheezing that is frequently diagnosed as asthma.

Study of the airways inflammation in sputum or the proximal airways usually reveals neutrophilic inflammation. Although there is significant phenotypic variation, tubular airways dilation consistent with bronchiectasis is a common finding in areas of panlobular emphysema in severely deficient AATD. Other phenotypes of varicose and saccular bronchiectasis have been described.

Since AAT may impact the course of bacterial, mycobacterial and viral clearance, future studies of the airway microbiota will inform whether airway pathogens are responsible for some pulmonary AATD phenotypes. Whether airways disease improves with AAT augmentation therapy remains unknown.

Pediatric Patients with Asthma: A High-Risk Population for Subsequent Hospitalization.

Asthma is one of the most common chronic conditions among children and is one of the leading causes for pediatric hospitalizations. More evidence is needed to clarify the risks of repeat hospitalization and the underlying factors contributing to adverse health outcomes among pediatric patients hospitalized with asthma.

The purpose of this study was to examine the risk of subsequent hospitalizations among pediatric patients hospitalized with asthma compared to a reference cohort of children hospitalized for all other diagnoses.

Methods. The Washington State (WA) Comprehensive Hospital Abstract Reporting System (CHARS) was used to obtain data for the study. Data describing 81,946 hospitalized pediatric patients admitted from 2004-2008 were available. The risk of subsequent hospitalization among children admitted for asthma as compared to a reference cohort was examined.

Results. The asthma cohort had a 33% (HR= 1.33 [99% confidence interval (CI) 1.21-1.46]; p < 0.001) increased risk of subsequent hospitalization from 2004-2008. Children in the asthma cohort under the age of 13 years demonstrated a significant increased risk of subsequent hospitalization as compared to the age matched reference cohort of children without asthma. Those in the asthma cohort who were 3-5 years old demonstrated the highest risk (50%) of subsequent hospitalization (HR= 1.50 [99% CI 1.23-1.83]; p < 0.001).

Conclusions. Study results can be utilized in the development of appropriate interventions aimed at preventing and reducing hospital admissions, improving patient care, decreasing overall costs, and lessening complications among pediatric patients with asthma.

Physiotherapy in asthma - seeking consensus.

The evidence base for or against physiotherapy interventions in adults with asthma remains ambiguous, and there are discrepancies between different clinical practice guidelines.

We evaluated the level of agreement between the recommendations about physiotherapy for adults with asthma in two major clinical practice guidelines: the Global Initiative for Asthma (GINA 2011) and the British Thoracic Society and the Association of Chartered Physiotherapists in Respiratory Care (BTS/ACPRC 2009).

Methods. We used the AGREE II instrument to assess the methodological rigour of the guideline development, the AMSTAR tool and the PEDro scale to assess the methodological quality of systematic reviews and clinical trials included in the analysed documents. Additionally, we compared the reference lists of the analysed sections to establish the overlap in included primary and secondary studies.

Results. We observed no agreement between the two guidelines in the choice of source research articles. Only 2 studies out of 18 used in BTS guidelines were used in the GINA. The reason why GINA developers did not use the body of evidence included in BTS is not clear. Three independent investigators indicated higher scores in all domains of the AGREE II in the BTS/ACPRC document in comparison with the GINA guidelines.

Conclusions. The significant differences in the content and development processes of the examined sections of the two guidelines suggest the need for more frequent and careful updating or directing the readers of the GINA to the BTS/ ACPRC, a guideline addressing specifically and more comprehensively physiotherapy interventions in asthma.

The contribution of goal specificity to goal achievement in collaborative goal setting for the management of asthma.

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Goal setting was investigated as part of an implementation trial of an asthma management service (PAMS) conducted in 96 Australian community pharmacies. Patients and pharmacists identified asthma-related issues of concern to the patient and collaboratively set goals to address these. Although goal setting is commonly integrated into disease state management interventions, the nature of goals, and their contribution to goal attainment and health outcomes are not well understood.

OBJECTIVES: To identify and describe:

1) goals set collaboratively between adult patients with asthma and their pharmacist,
2) goal specificity and goal achievement, and

3) describe the relationships between specificity, achievement, asthma control and asthma-related quality of life.

METHODS: Measures of goal specificity, and goal achievement were developed and applied to patient data records. Goals set were thematically analyzed into goal domains. Proportions of goals set, goals achieved and their specificity were calculated. Correlational and regression analyses were undertaken to determine the relationships between goal specificity, goal achievement, asthma control and asthma-related quality of life.

RESULTS: Data were drawn from 498 patient records. Findings showed that patients set a wide range and number of asthma-related goals (N = 1787) and the majority (93%) were either achieved or being working toward by the end of the study. Goal achievement was positively associated with specific and moderately specific goals, but not non-specific goals. However, on closer inspection, an inconsistent pattern of relationships emerged as a function of goal domain. Findings also showed that goal setting was associated with end-of-study asthma control but not to asthma-related quality of life.

CONCLUSIONS: Pharmacists can help patients to set achievable and specific asthma management goals, and these have the potential to directly impact health outcomes such as asthma control. Goal specificity appears to be an important feature in the achievement of goals, but other factors may also play a role.

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