- The number of ILC2 is increased in women with asthma compared to men with asthma
- Sex hormones regulate IL-2-dependent ILC2 proliferation and cytokine expression
- Testosterone intrinsically and extrinsically attenuates ILC2 airway inflammation
Early diagnosis of community-acquired pneumonia (CAP) is essential to reduce the total burden of this disease. Traditionally, chest radiography (CR) is used to identify true CAP. However, CR is not a perfect diagnostic test for CAP. The use of lung ultrasonography (LUS) has been suggested as an alternative to overcome the problems associated with CR and increase the feasibility and accuracy of CAP diagnosis. LUS has largely been used for the diagnosis of several lung problems, including CAP, in adult patients with satisfactory results. Experience with LUS in children has grown over recent years. The main aim of this paper is to discuss the advantages and limits of LUS in the diagnosis of paediatric CAP.
The presence of a consolidation pattern during LUS may represent pneumonia or atelectasis, although this conclusion is operator dependent. An overall agreement between LUS and CR was observed in most of the studies that were examined. In most reports where a disagreement between the two methods was found, CR was not able to identify the cases that were correctly diagnosed by LUS, particularly when CR was performed only with postero-anterior/antero-posterior projection and consolidation was observed in lung areas that are poorly visualized by CR. However, the lack of standardized LUS methods is problematic. Finally, the real advantage of LUS for the diagnosis of CAP in children remains unclear.
LUS is an interesting diagnostic modality that appears a useful first imaging test in children with suspected CAP. However, the methods used to perform LUS in children are not precisely standardized, and the diagnosis of interstitial CAP is inaccurate. Further studies are needed before LUS can be routinely used in everyday paediatric practice.
Rachel Knightly, Stephen J Milan, Rodney Hughes, Jennifer A Knopp-Sihota, Brian H Rowe, Rebecca Normansell, Colin Powell
Asthma exacerbations can be frequent and range in severity from mild to life-threatening. The use of magnesium sulfate (MgSO₄) is one of numerous treatment options available during acute exacerbations. While the efficacy of intravenous MgSO₄ has been demonstrated, the role of inhaled MgSO₄ is less clear.
To determine the efficacy and safety of inhaled MgSO₄ administered in acute asthma.
Specific aims: to quantify the effects of inhaled MgSO₄ I) in addition to combination treatment with inhaled β₂-agonist and ipratropium bromide; ii) in addition to inhaled β₂-agonist; and iii) in comparison to inhaled β₂-agonist.
We identified randomised controlled trials (RCTs) from the Cochrane Airways Group register of trials and online trials registries in September 2017. We supplemented these with searches of the reference lists of published studies and by contact with trialists.
RCTs including adults or children with acute asthma were eligible for inclusion in the review. We included studies if patients were treated with nebulised MgSO₄ alone or in combination with β₂-agonist or ipratropium bromide or both, and were compared with the same co-intervention alone or inactive control.
Data collection and analysis
Two review authors independently assessed trial selection, data extraction and risk of bias. We made efforts to collect missing data from authors. We present results, with their 95% confidence intervals (CIs), as mean differences (MDs) or standardised mean differences (SMDs) for pulmonary function, clinical severity scores and vital signs; and risk ratios (RRs) for hospital admission. We used risk differences (RDs) to analyse adverse events because events were rare.
Twenty-five trials (43 references) of varying methodological quality were eligible; they included 2907 randomised patients (2777 patients completed). Nine of the 25 included studies involved adults; four included adult and paediatric patients; eight studies enrolled paediatric patients; and in the remaining four studies the age of participants was not stated. The design, definitions, intervention and outcomes were different in all 25 studies; this heterogeneity made direct comparisons difficult. The quality of the evidence presented ranged from high to very low, with most outcomes graded as low or very low. This was largely due to concerns about the methodological quality of the included studies and imprecision in the pooled effect estimates.
Inhaled magnesium sulfate in addition to inhaled β₂-agonist and ipratropium
We included seven studies in this comparison. Although some individual studies reported improvement in lung function indices favouring the intervention group, results were inconsistent overall and the largest study reporting this outcome found no between-group difference at 60 minutes (MD −0.3 % predicted peak expiratory flow rate (PEFR), 95% CI −2.71% to 2.11%). Admissions to hospital at initial presentation may be reduced by the addition of inhaled magnesium sulfate (RR 0.95, 95% CI 0.91 to 1.00; participants = 1308; studies = 4; I² = 52%) but no difference was detected for re-admissions or escalation of care to ITU/HDU. Serious adverse events during admission were rare. There was no difference between groups for all adverse events during admission (RD 0.01, 95% CI −0.03 to 0.05; participants = 1197; studies = 2).
Inhaled magnesium sulfate in addition to inhaled β₂-agonist
We included 13 studies in this comparison. Although some individual studies reported improvement in lung function indices favouring the intervention group, none of the pooled results showed a conclusive benefit as measured by FEV1 or PEFR. Pooled results for hospital admission showed a point estimate that favoured the combination of MgSO₄ and β₂-agonist, but the confidence interval includes the possibility of admissions increasing in the intervention group (RR 0.78, 95% CI 0.52 to 1.15; participants = 375; studies = 6; I² = 0%). There were no serious adverse events reported by any of the included studies and no between-group difference for all adverse events (RD −0.01, 95% CI −0.05 to 0.03; participants = 694; studies = 5).
Inhaled magnesium sulfate versus inhaled β₂-agonist
We included four studies in this comparison. The evidence for the efficacy of β₂-agonists in acute asthma is well-established and therefore this could be considered a historical comparison. Two studies reported a benefit of β₂-agonist over MgSO₄ alone for PEFR and two studies reported no difference; we did not pool these results. Admissions to hospital were only reported by one small study and events were rare, leading to an uncertain result. No serious adverse events were reported in any of the studies in this comparison; one small study reported mild to moderate adverse events but the result is imprecise.
Treatment with nebulised MgSO₄ may result in modest additional benefits for lung function and hospital admission when added to inhaled β₂-agonists and ipratropium bromide, but our confidence in the evidence is low and there remains substantial uncertainty. The recent large, well-designed trials have generally not demonstrated clinically important benefits. Nebulised MgSO₄ does not appear to be associated with an increase in serious adverse events. Individual studies suggest that those with more severe attacks and attacks of shorter duration may experience a greater benefit but further research into subgroups is warranted.
Despite including 24 trials in this review update we were unable to pool data for all outcomes of interest and this has limited the strength of the conclusions reached. A core outcomes set for studies in acute asthma is needed. This is particularly important in paediatric studies where measuring lung function at the time of an exacerbation may not be possible. Placebo-controlled trials in patients not responding to standard maximal treatment, including inhaled β₂-agonists and ipratropium bromide and systemic steroids, may help establish if nebulised MgSO₄ has a role in acute asthma. However, the accumulating evidence suggests that a substantial benefit may be unlikely.Summary PDF
Breathing exercises taught by a physiotherapist in person or on DVD both improved the quality of life of adults with poorly controlled asthma to a small but similar extent. The DVD was the cheapest option, and it could lead to inexpensive internet delivery in the future.
This NIHR-funded trial recruited 655 UK adults with poorly controlled asthma. It showed about 63% of those receiving the breathing exercises had clinically important improvements in their asthma-related quality of life over a year, compared to 56% who improved receiving usual care.
Exercises did not improve formally measured lung function, suggesting the underlying biology of the asthma was unchanged.
The findings imply that breathing exercise programmes – currently recommended in the 2016 British guideline on the management of asthma when delivered by a physiotherapist – may be equally effective, and cheaper when delivered via DVD (or another video).
Jacqueline-Yvonne Cephus, Matthew T. Stier, Hubaida Fuseini, Jeffrey A. Yung, Shinji Toki, Melissa H. Bloodworth, Weisong Zhou, Kasia Goleniewska, and others
Sex hormones regulate many autoimmune and inflammatory diseases, including asthma. As adults, asthma prevalence is 2-fold greater in women compared to men. The number of group 2 innate lymphoid cells (ILC2) is increased in patients with asthma, and we investigate how testosterone attenuates ILC2 function. In patients with moderate to severe asthma, we determine that women have an increased number of circulating ILC2 compared to men. ILC2 from adult female mice have increased IL-2-mediated ILC2 proliferation versus ILC2 from adult male mice, as well as pre-pubescent females and males. Further, 5α-dihydrotestosterone, a hormone downstream of testosterone, decreases lung ILC2 numbers and IL-5 and IL-13 expression from ILC2. In vivo, testosterone attenuated Alternaria-extract-induced IL-5+ and IL-13+ ILC2 numbers and lung eosinophils by intrinsically decreasing lung ILC2 numbers, as well as by decreasing expression of IL-33 and thymic stromal lymphopoietin (TSLP), ILC2-stimulating cytokines. Collectively, these findings provide a foundational understanding of sexual dimorphism in ILC2 function.