Heather Powell

A meta-analysis of adverse perinatal outcomes in women with asthma

Please cite this paper as: Murphy V, Namazy J, Powell H, Schatz M, Chambers C, Attia J, Gibson P. A meta‐analysis of adverse perinatal outcomes in women with asthma. BJOG 2011;118:1314–1323.

The Asthma Control Test and Asthma Control Questionnaire for assessing asthma control: Systematic review and meta-analysis.

BACKGROUND Currently, the cornerstone of asthma management is the achievement and maintenance of optimal asthma control, but the diagnostic performances of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) have not been evaluated systematically. OBJECTIVE We explored the diagnostic performances of and statistically compared the ACT and ACQ. METHODS Studies that examined the accuracy of the ACT, ACQ, or both in the assessment of asthma control were found by searching PubMed, CENTRAL, Web of Science, Ovid, and Embase. Summary estimates of sensitivity, specificity, and diagnostic odds ratios for the different levels of asthma control were determined by using bivariate random-effects models and hierarchical summary receiver operating characteristic models. RESULTS Twenty-one studies with 11,141 subjects assessed with the ACT and 12,483 assessed with the ACQ were identified. The ACT had good diagnostic accuracy for assessment of controlled and not well-controlled asthma, and the ACQ (ACQ-7 and ACQ-6) had good diagnostic accuracy for assessment of not well-controlled asthma at prespecified cutoff points. The ACT and ACQ had significant differences in the assessment of controlled and not well-controlled asthma after adjusting for potential factors (P = .001 and P = .015). For assessment of uncontrolled asthma, the ACT had poor accuracy, with a hierarchical summary receiver operating characteristic area under the curve of 0.69, and the cutoff point for the ACQ has not been established. CONCLUSION The ACT is preferable to the ACQ in clinical practice, and the ACQ requires further cross-validation. Moreover, neither the ACT nor the ACQ is useful for the assessment of uncontrolled asthma.

Relationship between induced sputum eosinophils and the clinical pattern of childhood asthma

Background: The relationship between the clinical pattern of asthma and airway inflammation in childhood asthma is poorly characterised, yet underpins the treatment recommendations in current asthma guidelines. A study was undertaken to examine the relationship between airway inflammation and clinical asthma in children. Methods: Children with asthma (n=146) and healthy controls (C, n=37) were recruited from primary and specialist clinics. Sputum induction and hypertonic saline challenge were performed. Results: As the frequency of asthma episodes in the past 12 months increased, there were significant increases in sputum eosinophils (median; infrequent episodic (IE) 1.5%, frequent episodic (FE) 2.3%, persistent (P) 3.8%, control (C) 1.0%; p=0.002), sputum eosinophil cationic protein (ECP) (IE 113 ng/ml, FE 220, P 375, C 139; p=0.003), and desquamated bronchial epithelial cells (IE 2.0%, FE 6.0%, P 5.0%, C 2.5%; p=0.04). Treatment intensity was also associated with increased sputum eosinophils (p=0.005). The relationships between other severity markers (current symptoms, lung function) were less strong. Conclusion: Children with more frequent episodes of clinical asthma exhibit increasing airway inflammation that is characterised by sputum eosinophilia and bronchial epithelial desquamation. The results support clinical assessment by frequency of wheezing episodes over the past 12 months when determining anti-inflammatory treatment requirements, and indicate that current symptoms are determined by mechanisms in addition to sputum eosinophilia.

Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma: Proof of concept

Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3×7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV1 and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.

Identification of Novel Diagnostic Biomarkers for Asthma and Chronic Obstructive Pulmonary Disease

RATIONALE Proteomics may identify a useful panel of biomarkers for identification of asthma and chronic obstructive pulmonary disease (COPD). OBJECTIVES To conduct an unsupervised analysis of peripheral blood proteins in well-characterized subjects with asthma and COPD, and identify and validate a biomarker panel for disease discrimination. METHODS Two-dimensional difference gel electrophoresis was used to separate plasma proteins from healthy control subjects, stable patients with asthma, and individuals with COPD. Candidate protein markers were identified by matrix assisted laser desorption ionization time of flight mass spectrometry and subsequently validated in two populations via immunoassay. A panel of four biomarkers was selected and their ability to distinguish between groups was assessed in isolation and in combination in two separate validation populations. MEASUREMENTS AND MAIN RESULTS Seventy-two protein spots displayed significantly different expression levels between the three subject groupings (P < 0.05). Fifty-eight were positively identified, representing 20 unique proteins. A panel of four biomarkers (α(2)-macroglobulin, haptoglobin, ceruloplasmin, and hemopexin) was able to discriminate with statistical significance between the clinical groups of patients with asthma, patients with COPD, and control subjects, and these results were confirmed in a second clinical population of older adults with airflow obstruction. CONCLUSIONS Proteomics has identified novel biomarkers for asthma and COPD, and shown that the iron metabolism pathways and acute-phase response may be involved in the pathogenesis of airway disease. The panel of peripheral blood biomarkers has the potential to become an extremely useful addition to the clinical diagnosis and management of respiratory disease.

Full blood count parameters for the detection of asthma inflammatory phenotypes

In asthma, the airway inflammatory phenotype influences clinical characteristics and treatment response. Although induced sputum is the gold standard test for phenotyping asthma, a more accessible method is needed for clinical practice.

Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes

BACKGROUND Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms. OBJECTIVE This study aimed to identify and validate a sputum gene expression signature that discriminates asthma inflammatory phenotypes. METHODS An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients. A clinical validation study (n = 59 asthmatic patients) confirmed differential expression of key genes. A 6-gene signature was identified and evaluated for reproducibility (n = 30 asthmatic patients and n = 20 control subjects) and prediction of inhaled corticosteroid (ICS) response (n = 71 asthmatic patients). Receiver operating characteristic curves were calculated, and area under the curve (AUC) values were reported. RESULTS From 277 differentially expressed genes between asthma inflammatory phenotypes, we identified 23 genes that showed highly significant differential expression in both the discovery and validation populations. A signature of 6 genes, including Charcot-Leydon crystal protein (CLC); carboxypeptidase A3 (CPA3); deoxyribonuclease I-like 3 (DNASE1L3); IL-1β (IL1B); alkaline phosphatase, tissue-nonspecific isozyme (ALPL); and chemokine (C-X-C motif) receptor 2 (CXCR2), was reproducible and could significantly (P < .0001) discriminate eosinophilic asthma from other phenotypes, including patients with noneosinophilic asthma (AUC, 89.6%), paucigranulocytic asthma (AUC, 92.6%), or neutrophilic asthma (AUC, 91.4%) and healthy control subjects (AUC, 97.6%), as well as discriminating patients with neutrophilic asthma from those with paucigranulocytic asthma (AUC, 85.7%) and healthy control subjects (AUC, 90.8). The 6-gene signature predicted ICS response (>12% change in FEV1; AUC, 91.5%). ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with eosinophilic asthma. CONCLUSIONS A sputum gene expression signature of 6 biomarkers reproducibly and significantly discriminates inflammatory phenotypes of asthma and predicts ICS treatment response. This signature has the potential to become a useful diagnostic tool to assist in the clinical diagnosis and management of asthma.

Effects of asthma severity, exacerbations and oral corticosteroids on perinatal outcomes

This systematic review and meta-analysis sought to investigate whether asthma exacerbations, oral corticosteroid use or asthma severity are associated with prematurity and intrauterine growth restriction. Cohort studies published between 1975 and March 11, 2012 were considered for inclusion. 138 publications were identified for possible inclusion, and nine papers met the inclusion criteria, by reporting perinatal outcomes of interest (low birth weight, <2500 g), pre-term birth (<37 weeks gestation unless otherwise stated) and small for gestational age (<10th percentile for gestational age and sex) in groups of asthmatic patients stratified by history of exacerbations, oral corticosteroid use or asthma severity. Maternal asthma exacerbations and oral corticosteroid use had a significant effect on outcomes, including low birth weight (RR 3.02, 95% CI 1.87–4.89 and RR 1.41, 95% CI 1.04–1.93, respectively) and pre-term delivery (RR 1.54, 95% CI 0.89–2.69 and RR 1.51, 95% CI 1.15–1.98, respectively). Moderate-to-severe asthma during pregnancy was associated with an increased risk of small for gestational age (RR 1.24, 95% CI 1.15–1.35) and low birth weight (RR 1.15, 95% CI 1.05–1.26) infants. These data suggest that asthma exacerbations, oral corticosteroid use or asthma severity defined as moderate-to-severe may be associated with pre-term delivery, low birth weight, and small for gestational age infants. Further studies on the effect of maternal asthma control on perinatal outcomes are warranted.

The risk of congenital malformations, perinatal mortality and neonatal hospitalisation among pregnant women with asthma: a systematic review and meta-analysis.

There is conflicting literature on the effect of maternal asthma on congenital malformations and neonatal outcomes.

Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial

BACKGROUND Exacerbations of asthma cause a substantial global illness burden. Adults with uncontrolled persistent asthma despite maintenance treatment require additional therapy. Since macrolide antibiotics can be used to treat persistent asthma, we aimed to assess the efficacy and safety of oral azithromycin as add-on therapy in patients with uncontrolled persistent asthma on medium-to-high dose inhaled corticosteroids plus a long-acting bronchodilator. METHODS We did a randomised, double-blind, placebo controlled parallel group trial to determine whether oral azithromycin decreases the frequency of asthma exacerbations in adults (≥18 years) with symptomatic asthma despite current use of inhaled corticosteroid and long-acting bronchodilator, and who had no hearing impairment or abnormal prolongation of the corrected QT interval. Patients were randomly assigned (1:1) to receive azithromycin 500 mg or placebo three times per week for 48 weeks. Patients were centrally allocated using concealed random allocation from a computer-generated random numbers table with permuted blocks of 4 or 6 and stratification for centre and past smoking. Primary efficacy endpoints were the rate of total (severe and moderate) asthma exacerbations over 48 weeks and asthma quality of life. Data were analysed on an intention-to-treat basis. The trial is registered at the Australian and New Zealand Clinical Trials Registry (ANZCTR), number 12609000197235. FINDINGS Between June 12, 2009, and Jan 31, 2015, 420 patients were randomly assigned (213 in the azithromycin group and 207 in the placebo group). Azithromycin reduced asthma exacerbations (1·07 per patient-year [95% CI 0·85-1·29]) compared with placebo (1·86 per patient-year [1·54-2·18]; incidence rate ratio [IRR] 0·59 [95% CI 0·47-0·74]; p<0·0001). The proportion of patients experiencing at least one asthma exacerbation was reduced by azithromycin treatment (127 [61%] patients in the placebo group vs 94 [44%] patients in the azithromycin group, p<0·0001). Azithromycin significantly improved asthma-related quality of life (adjusted mean difference, 0·36 [95% CI 0·21-0·52]; p=0·001). Diarrhoea was more common in azithromycin-treated patients (72 [34%] vs 39 [19%]; p=0·001). INTERPRETATION Adults with persistent symptomatic asthma experience fewer asthma exacerbations and improved quality of life when treated with oral azithromycin for 48 weeks. Azithromycin might be a useful add-on therapy in persistent asthma. FUNDING National Health and Medical Research Council of Australia, John Hunter Hospital Charitable Trust.