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Long-Acting β2-Agonist Step-off in Patients With Controlled Asthma: Systematic Review With Meta-analysis.

Because of concerns about the safety of long-acting β2-agonist (LABA) use in patients with asthma, withdrawal of the LABA is recommended by the US Food and Drug Administration once asthma is controlled by combination therapy with a LABA and inhaled corticosteroid (ICS).

OBJECTIVE To perform a systematic review and meta-analysis assessing evidence supporting the discontinuation of LABA therapy once asthma control has been achieved with a combination of ICS and LABA.

DATA SOURCES MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched (through August 2010), references of identified studies and selected narrative review articles were evaluated, registries of clinical trials were reviewed, and manufacturers of LABAs were contacted.

STUDY SELECTION Randomized controlled trials of discontinuation of LABA therapy in patients with asthma controlled with a combination of ICS and LABA. DATA EXTRACTION Two reviewers independently screened each title and abstract in the initial searches and then the full text of each nominated article to extract data for analyses.

RESULTS Of 1492 screened articles, only 5 trials involving patients aged 15 years or older fulfilled a priori-specified inclusion criteria. Results did not favor the LABA step-off approach compared with no change in treatment. The LABA step-off regimen increased asthma impairment, with worse Asthma Quality of Life Questionnaire score (mean difference [95% CI], 0.32 [0.14-0.51] points lower); worse Asthma Control Questionnaire score (0.24 [0.13-0.35] points higher); fewer symptom-free days (9.15% [1.62%-16.69%] less); and greater risk of withdrawal from study resulting from lack of efficacy or loss of asthma control (risk ratio, 3.27 [2.16-4.96]). Risk of exacerbations and deaths after LABA step-off were not evaluable because of the small number of events and short duration of follow-up.

CONCLUSIONS Evidence suggests that discontinuing LABA therapy in adults and older children with asthma controlled with a combination of ICSs and LABAs results in increased asthma-associated impairment. Additional trials measuring all long-term patient-important outcomes are needed.

The measurement of lung volumes using body plethysmography: a comparison of methodologies.

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The measurement of lung volumes using body plethysmography: a comparison of methodologies.

Respir Care. 2012 Jul;57(7):1076-83

Authors: Borg BM, Thompson BR

Abstract
BACKGROUND: The statement of the American Thoracic Society and European Respiratory Society on the measurement of static lung volumes (SLV) suggests a preferred and alternate method for measuring and calculating SLV.
OBJECTIVE: To determine if differences in functional residual capacity (FRC), vital capacity (VC), residual volume (RV), and total lung capacity (TLC), obtained using preferred and alternate measurement and calculation methodologies, exist in a clinical setting.
METHODS: Patients attending for SLV at a hospital-based laboratory were recruited. Following spirometry, SLV was measured via body plethysmography, using the preferred and alternate methods in random order. Volumes were calculated using the preferred and alternate calculation methods. Subjects were classified according to standard ventilatory function interpretative strategies. Differences of the means between the measurement methods, and calculation methods were assessed.
RESULTS: One hundred eight data sets were analyzed. Significant, but small differences (< 150 mL) in the means for VC and TLC, and RV and TLC were found in the normal and restricted groups, respectively. No significant differences in SLV parameters were found in subjects with air-flow obstruction. Twelve of the 108 changed ventilatory function classification between methods, with the alternate method delivering a lower inspiratory capacity and TLC without a change in RV in 66% of this subgroup. Identical results were obtained when data were analyzed using both calculation methods.
CONCLUSIONS: Differences in FRC, VC, RV, and TLC obtained using the preferred and alternate measurement methodologies exist in the clinical setting in select classification groups and individuals. Differing calculation methods dependent on measurement method used may be unnecessary.

PMID: 22272788 [PubMed - indexed for MEDLINE]

Early administration of systemic corticosteroids reduces hospital admission rates for children with moderate and severe asthma exacerbation.

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Early administration of systemic corticosteroids reduces hospital admission rates for children with moderate and severe asthma exacerbation.

Ann Emerg Med. 2012 Jul;60(1):84-91.e3

Authors: Bhogal SK, McGillivray D, Bourbeau J, Benedetti A, Bartlett S, Ducharme FM

Abstract
STUDY OBJECTIVE: The variable effectiveness of clinical asthma pathways to reduce hospital admissions may be explained in part by the timing of systemic corticosteroid administration. We examine the effect of early (within 60 minutes [SD 15 minutes] of triage) versus delayed (>75 minutes) administration of systemic corticosteroids on health outcomes.
METHODS: We conducted a prospective observational cohort of children aged 2 to 17 years presenting to the emergency department with moderate or severe asthma, defined as a Pediatric Respiratory Assessment Measure (PRAM) score of 5 to 12. The outcomes were hospital admission, relapse, and length of active treatment; they were analyzed with multivariate logistic and linear regressions adjusted for covariates and potential confounders.
RESULTS: Among the 406 eligible children, 88% had moderate asthma; 22%, severe asthma. The median age was 4 years (interquartile range 3 to 8 years); 64% were male patients. Fifty percent of patients received systemic corticosteroids early; in 33%, it was delayed; 17% of children failed to receive any. Overall, 36% of patients were admitted to the hospital. Compared with delayed administration, early administration reduced the odds of admission by 0.4 (95% confidence interval 0.2 to 0.7) and the length of active treatment by 0.7 hours (95% confidence interval -1.3 to -0.8 hours), with no significant effect on relapse. Delayed administration was positively associated with triage priority and negatively with PRAM score.
CONCLUSION: In this study of children with moderate or severe asthma, administration of systemic corticosteroids within 75 minutes of triage decreased hospital admission rate and length of active treatment, suggesting that early administration of systemic corticosteroids may allow for optimal effectiveness.

PMID: 22410507 [PubMed - indexed for MEDLINE]

Serologic allergic bronchopulmonary aspergillosis (ABPA-S): long-term outcomes.

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Serologic allergic bronchopulmonary aspergillosis (ABPA-S): long-term outcomes.

Respir Med. 2012 Jul;106(7):942-7

Authors: Agarwal R, Garg M, Aggarwal AN, Saikia B, Gupta D, Chakrabarti A

Abstract
BACKGROUND AND AIM: ABPA is radiologically classified on the presence or absence of central bronchiectasis (CB) as ABPA-CB and serologic ABPA (ABPA-S) respectively. Few studies have described the follow-up of patients with ABPA-S. The aim of this retrospective study was to describe the outcomes of ABPA-S.
METHODS: Patients were diagnosed as ABPA-S if they met all the following criteria: asthma, immediate cutaneous hyperreactivity to Aspergillus fumigatus antigen, total IgE levels >1000 IU/mL, A. fumigatus specific IgE levels >0.35 kUA/L and normal HRCT of the chest. They were treated with glucocorticoids and followed up with history, physical examination, chest radiograph and total IgE levels every 6 weeks to 3 months. In addition, an annual spirometry and a biennial HRCT chest were performed in all patients.
RESULTS: Of the 55 patients with ABPA-S, 41 (17 men, 24 women; mean age, 38.3 years) consented for performance of repeat HRCT scans. The median duration of asthma prior to diagnosis of ABPA was six years. The duration of follow-up ranged from 24 to 77 months with the mean (SD) follow-up duration being 43.7 (10.1) months. There was improvement in FEV(1) but not the FVC values during the follow-up period (p values = 0.001 and 0.5 for FEV(1) and FVC respectively). There was no development of CB in any patient. Sixteen patients had a relapse during the follow-up period, and six patients were classified as glucocorticoid-dependent ABPA.
CONCLUSIONS: Although relapses are frequently seen, the long-term outcome of ABPA-S is good with no patient developing CB.

PMID: 22445696 [PubMed - indexed for MEDLINE]

Comparison of American and European practices in the management of patients with primary immunodeficiencies.

Primary immunodeficiency diseases (PIDs) comprise a heterogeneous group of rare disorders. This study was devised in order to compare management of these diseases in the northern hemisphere, given the variability of practice among clinicians in North America. The members of two international societies for clinical immunologists were asked about their management protocols in relation to their PID practice.

An anonymous internet questionnaire, used previously for a survey of the American Academy of Allergy, Asthma and Immunology (AAAAI), was offered to all full members of the European Society for Immunodeficiency (ESID). The replies were analysed in three groups, according to the proportion of PID patients in the practice of each respondent; this resulted in two groups from North America and one from Europe.

The 123 responses from ESID members (23·7%) were, in the majority, very similar to those of AAAAI respondents, with > 10% of their practice devoted to primary immunodeficiency. There were major differences between the responses of these two groups and those of the general AAAAI respondents whose clinical practice was composed of < 10% of PID patients. These differences included the routine use of intravenous immunoglobulin therapy (IVIg) for particular types of PIDs, initial levels of IVIg doses, dosing intervals, routine use of prophylactic antibiotics, perceptions of the usefulness of subcutaneous immunoglobulin therapy (SCIg) and of the risk to patients' health of policies adopted by health-care funders.

Differences in practice were identified and are discussed in terms of methods of health-care provision, which suggest future studies for ensuring continuation of appropriate levels of immunoglobulin replacement therapies.

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