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Introduction: Little is known about the relationship of whole‐grain intake with dietary fatty acids intake. The present study aimed to assess the whole‐grain intake and its relationships with dietary fatty acids intake among multiethnic schoolchildren in Kuala Lumpur, Malaysia. Methods: This cross‐sectional study was conducted among 392 schoolchildren aged 9–11 years, cluster sampled from five randomly selected schools in Kuala Lumpur. Whole‐grain and fatty acids intakes were assessed by 3‐day, 24‐h diet recalls. All whole‐grain foods were considered irrespective of the amount of whole grain they contained. Results: In total, 55.6% (n = 218) were whole‐grain consumers. Mean (SD) daily intake of whole grain in the total sample was 5.13 (9.75) g day−1. In the whole‐grain consumer's only sample, mean (SD) intakes reached 9.23 (11.55) g day−1. Significant inverse associations were found between whole‐grain intake and saturated fatty acid (SAFA) intake (r = −0.357; P < 0.001), monosaturated fatty acid (MUFA) (r = −0.373; P < 0.001) and polyunsaturated fatty acid (PUFA) (r = −0.307; P < 0.001) intake. Furthermore, whole‐grain intake was a significant predictor of SAFA (β = −0.077; P = 0.004), MUFA (β = −0.112; P = <0.001) and PUFA (β = −0.202; P = <0.001) intakes, after controlling for sex, age and ethnicity. Conclusions: Whole‐grain intake in Malaysia was well below recommendations. Schoolchildren who consumed higher whole grain tend to reduce fat intake; however, it would also reduce the SAFA, MUFA and PUFA intakes. Future collaboration may be conducted between industry, government and universities to promote unsaturated fatty acids‐rich foods and whole‐grain food, although not to promote processed whole‐grain foods with a high sugar and salt content. [ABSTRACT FROM AUTHOR]

Abstract: The care of patients with difficult‐to‐control asthma (“difficult asthma”) is challenging and costly. Despite high‐intensity asthma treatment, these patients experience poor asthma control and face the greatest risk of asthma morbidity and mortality. Poor asthma control is often driven by severe asthma biology, which has appropriately been the focus of intense research and phenotype‐driven therapies. However, it is increasingly apparent that extra‐pulmonary comorbidities also contribute substantially to poor asthma control and a heightened disease burden. These comorbidities have been proposed as “treatable traits” in chronic airways disease, adding impetus to their evaluation and management in difficult asthma. In this review, eight major asthma‐related comorbidities are discussed: rhinitis, chronic rhinosinusitis, gastroesophageal reflux, obstructive sleep apnoea, vocal cord dysfunction, obesity, dysfunctional breathing and anxiety/depression. We describe the prevalence, impact and treatment effects of these comorbidities in the difficult asthma population, emphasizing gaps in the current literature. We examine the associations between individual comorbidities and highlight the potential for comorbidity clusters to exert combined effects on asthma outcomes. We conclude by outlining a pragmatic clinical approach to assess comorbidities in difficult asthma. [ABSTRACT FROM AUTHOR]

Summary: Background: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. Objective: To compare workplace productivity—absenteeism and presenteeism—and impairment in daily activities in severe and non‐severe asthma over time and identify characteristics associated with presenteeism in severe asthma. Methods: The Severe Asthma Web‐based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non‐severe asthma were enrolled (18‐88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed‐up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self‐reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. Results: At baseline, 61.4% of participants with severe asthma and 66.2% with non‐severe asthma under 65 years were employed. At younger ages (30‐50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past‐year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non‐severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma‐related quality of life and symptoms of depression or anxiety (P < .01). Conclusion and clinical relevance: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age. [ABSTRACT FROM AUTHOR]

Purpose: Clinical outcomes prognostic markers are awaited in clear-cell renal carcinoma (ccRCC) to improve patient-tailored management and to assess six different markers' influence on clinical outcomes from ccRCC specimen and their incremental value combined with TNM staging. Materials and methods: This is a retrospective, multicenter study. One hundred and forty-three patients with pT1b-pT3N0M0 ccRCC were included. Pathology specimens from surgeries were centrally reviewed, mounted on a tissue micro-array and stained with six markers: CAIX, c-MYC, Ki67, p53, vimentin and PTEN. Images were captured through an Ultra Fast Scanner. Tumor expression was measured with Image Pro Plus. Cytoplasmic markers (PTEN, CAIX, vimentin, c-MYC) were expressed as surface percentage of expression. Nuclear markers (Ki67, p53) were expressed as number of cells/mm. Clinical data and markers expression were compared with clinical outcomes. Each variable was included in the Cox proportional multivariate analyses if p < 0.10 on univariate analyses. Discrimination of the new marker was calculated with Harrell's concordance index. Results: At median follow-up of 63 months (IQR 35.0-91.8), on multivariate analysis, CAIX under-expression and vimentin over-expression were associated with worse survival (recurrence, specific and overall survival). A categorical marker CAIX-/Vimentin+ with cutoff points for CAIX and vimentin of 30 and 50 %, respectively, was designed. The new CAIX-/Vimentin+ marker presented a good concordance and comparable calibration to the reference model. Limitations are the retrospective design, the need for external validation and the large study period. Conclusion: Using an automated technique of measurement, CAIX and vimentin are independent predictors of clinical outcomes in ccRCC. [ABSTRACT FROM AUTHOR]

Background Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry ( AXR). Objectives To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. Methods Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). Results Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 ( IQR 632, 1747) IU/mL vs. 209 ( IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 ( IQR 650, 750) mg] compared to within-range participants [450 ( IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire ( ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire ( AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second ( FEV1) improved among above-range participants. There was no difference in response between above-range and within-range participants. Above-range participants due to either IgE alone or IgE and weight had similar improvements in ACQ-5, AQLQ and FEV1. Conclusions and Clinical Relevance Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg. [ABSTRACT FROM AUTHOR]

Background There is strong evidence that direct ultrasound localisation for pleural aspiration reduces complications, but this practice is not universal in Australia and New Zealand. Aims To describe the current utilisation and logistical barriers to the use of direct ultrasound localisation for pleural aspiration by respiratory physicians from Australia and New Zealand, and to determine the cost benefits of procuring equipment and training resources in chest ultrasound. Methods We surveyed all adult respiratory physician members of the Thoracic Society of Australia and New Zealand regarding their use of direct ultrasound localisation for pleural aspiration. We performed a cost-benefit analysis for acquiring bedside ultrasound equipment and estimated the capacity of available ultrasound training. Results One hundred and forty-six of 275 respiratory physicians responded (53% response). One-third (33.6%) of respondents do not undertake direct ultrasound localisation. Lack of training/expertise (44.6%) and lack of access to ultrasound equipment (41%) were the most frequently reported barriers to performing direct ultrasound localisation. An average delay of 2 or more days to obtain an ultrasound performed in radiology was reported in 42.7% of respondents. Decision-tree analysis demonstrated that clinician-performed direct ultrasound localisation for pleural aspiration is cost-beneficial, with recovery of initial capital expenditure within 6 months. Ultrasound training infrastructure is already available to up-skill all respiratory physicians within 2 years and is cost-neutral. Conclusion Many respiratory physicians have not adopted direct ultrasound localisation for pleural aspiration because they lack equipment and expertise. However, purchase of ultrasound equipment is cost-beneficial, and there is already sufficient capacity to deliver accredited ultrasound training through existing services. [ABSTRACT FROM AUTHOR]

Clinician-performed chest ultrasound is rapidly entering clinical practice in the fields of intensive care, respiratory medicine and acute medicine. Ultrasound is clearly useful in the diagnosis and characterisation of pleural diseases. It is also critical in improving the safety of pleural interventions. More recently, attention has also focused on the use of lung ultrasound. While the normal aerated lung is not well imaged by ultrasound, lung pathology reaching the pleura often provides an 'acoustic window' for a number of lung conditions. Lung ultrasound is useful to diagnose pneumothorax, interstitial and alveolar lung abnormalities, and pleurally based lung masses. There is some evidence that integrating routine chest ultrasound into clinical practice has benefit in the emergency and intensive care settings. In the future, chest ultrasound is likely to become an essential physician skill, and training requirements are evolving in light of current developments. [ABSTRACT FROM AUTHOR]

Background/Aim: We determined current practice among Australasian thoracic physicians in the mediastinal staging of non-small-cell lung cancer (NSCLC). We focused on the availability of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) and constraints to its use, as there has been no systematic analysis regarding the availability and uptake of this new technology among thoracic physicians. Methods: Physician members of the Thoracic Society of Australia and New Zealand were emailed a survey seeking their current approach to three scenarios requiring mediastinal staging of NSCLC. Respondents were also asked for their preferred investigation for each scenario if any current constraints were removed. Relevant demographic information was sought. Results: We received 164 responses from 512 Australasian physicians (34%). Without constraints, EBUS-TBNA was the preferred investigation for all three clinical scenarios, but only 33% of respondents had access to EBUS-TBNA. Constraints included lack of availability and lack of expertise. Reduced EBUS-TBNA access was associated with a number of clinician factors. Conclusions: Australasian thoracic physicians prefer EBUS-TBNA for the mediastinal staging of NSCLC, but access to EBUS-TBNA services is limited. We recommend targeted measures to improve access to EBUS-TBNA use and optimise mediastinal staging of NSCLC. [ABSTRACT FROM AUTHOR]

Background: Performance of linear probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging non-small-cell lung cancer has been extensively studied. Alternate indications for its use are less well characterised, and performance in other clinical settings may differ. Methods: We examined a prospectively collected cohort comprising the first 215 patients undergoing EBUS-TBNA at our institution. Patients were analysed according to the clinical and radiological indication for referral. We also examined the effect of the procedural learning curve on diagnostic sensitivity. Results: A total of 215 patients underwent 216 EBUS-TBNA procedures. EBUS-TBNA returned adequate tissue for cytopathological analysis in 202 of 216 procedures (94%). Overall sensitivity for detection of malignancy was 0.92 (95% confidence interval 0.86-0.96); however, this varied according to the primary indication for EBUS-TBNA. Diagnostic sensitivity was high among all sub-groups, but the negative predictive value varied depending on the clinical indication for the procedure. We estimate 104 invasive surgical procedures and 32 inpatient admissions were avoided by use of EBUS-TBNA. Significant improvement in diagnostic performance was seen after 20 procedures were completed, and diagnostic accuracy did not peak until after 50 procedures. Conclusions: EBUS-TBNA is able to confirm accurately histologically a large number of disease processes, both malignant and benign, in all clinical indications studied. The procedure is safe even when carried out by proceduralists with minimal prior experience. Diagnostic performance continues to improve beyond 50 cases carried out. [ABSTRACT FROM AUTHOR]

Chronic severe asthma remains a challenging clinical problem despite the availability of modern treatments. Relative corticosteroid insensitivity is present in severe asthma and may contribute to continuing disease severity. Advances in the understanding of molecular mechanisms underlying corticosteroid insensitivity may yield new therapeutic targets. Furthermore, aetiological factors for corticosteroid insensitivity have been identified and these may be amenable to modification. [ABSTRACT FROM AUTHOR]

Background About 5–10% of patients with asthma suffer from poorly-controlled disease despite corticosteroid (CS) therapy. Objective We determined whether there were any differences in inflammatory biomarkers between severe and non-severe asthma patients. Methods Nineteen severe and 20 non-severe asthma patients were recruited and underwent collection of induced sputum, bronchoalveolar lavage (BAL) fluid and bronchial biopsies. Results Biopsy results showed no differences in eosinophils (major basic protein positive), neutrophils, macrophages, T cells and mast cells in the bronchial submucosa. However, subbasement membrane (SBM) thickness and smooth muscle area were increased in the biopsies. No significant differences were observed in the induced sputum inflammatory cells. In BAL fluid, there was a significant increase in neutrophils but a significant decrease in macrophages. Eosinophil counts were non-significantly increased threefold in both sputum and BAL in severe asthma. Levels of IL-8 and IL-13 in sputum supernatants were similar in both groups of asthma patients. There was a significant inverse correlation between post-bronchodilator forced expiratory volume in 1 s and provocative concentration of methacholine causing a 20% fall in FEV1 with SBM thickness. Conclusion Differences in inflammatory cells were observed mainly in terms of increased neutrophils and reduction in macrophage numbers in BAL fluid with a trend towards increased eosinophils in severe asthma compared with non-severe asthma. However, the most notable features are the increase in features of airway wall remodelling of SBM thickness and smooth muscle area. [ABSTRACT FROM AUTHOR]

Background: About 5-10% of patients with asthma suffer from poorly controlled disease despite corticosteroid (CS) treatment, which may indicate the presence of CS insensitivity. A study was undertaken to determine whether relative CS insensitivity is present in alveolar macrophages from patients with severe asthma and its association with p38 mitogen-activated protein kinase (MAPK) activation and MAPK phosphatase-1 (MKP-1).Methods: Fibreoptic bronchoscopy and bronchoalveolar lavage (BAL) were performed in 20 patients with severe asthma and 19 with non-severe asthma and, for comparison, in 14 normal volunteers. Alveolar macrophages were exposed to lipopolysaccharide (LPS, 10 mug/ml) and dexamethasone (10(-8) and 10(-6) M). Supernatants were assayed for cytokines using an ELISA-based method. p38 MAPK activity and MKP-1 messenger RNA expression were assayed in cell extracts.Results: The inhibition of LPS-induced interleukin (IL)1beta, IL6, IL8, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1alpha release by dexamethasone (10(-6) M) was significantly less in macrophages from patients with severe asthma than in macrophages from patients with non-severe asthma. There was increased p38 MAPK activation in macrophages from patients with severe asthma. MKP-1 expression induced by dexamethasone and LPS, expressed as a ratio of LPS-induced expression, was reduced in severe asthma.Conclusion: Alveolar macrophages from patients with severe asthma demonstrate CS insensitivity associated with increased p38 MAPK activation that may result from impaired inducibility of MKP-1. [ABSTRACT FROM AUTHOR]

Background: Bronchiectasis is a suppurative airway disease characterised by persistent cough and sputum production associated with bronchial dilatation. A study was undertaken to determine whether cough sensitivity is increased in bronchiectatic patients.Methods: Twenty two patients with bronchiectasis and 20 healthy non-smoking controls matched for age and sex were recruited into the study. Quality of life (Leicester Cough Questionnaire score), total cough symptom score, and extent of bronchiectasis on HRCT scans were recorded. Cough sensitivity was assessed using incremental inhalation of capsaicin concentrations; the concentration at which 5 or more coughs occurred (C5) was recorded.Results: Patients with bronchiectasis had increased sensitivity to capsaicin compared with controls (mean (SE) log10 C5 1.22 (0.20) v 1.89 (0.21); p<0.03). Capsaicin sensitivity correlated positively with the Leicester Cough Questionnaire score (r = 0.64; p = 0.005) and inversely with the total cough symptom score (r = -0.58; p = 0.004), but not with the extent of the disease. It also correlated with forced expiratory volume in 1 second (FEV1) in litres (r = 0.58; p = 0.005) but not with FEV1 % predicted. Capsaicin sensitivity was not related to the presence of infected sputum or to corticosteroid or bronchodilator use.Conclusions: : Patients with bronchiectasis have a sensitive cough reflex which reflects the severity of cough symptoms. A measure of cough severity could be part of health assessment for patients with bronchiectasis. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Patients with severe asthma have a poor therapeutic response to corticosteroid therapy, and corticosteroid responsiveness cannot be easily measured in these patients. We hypothesized that this poor response is associated with a reduced effect of corticosteroids to inhibit cytokine release from activated peripheral blood mononuclear cells (PBMCs).Methods: Patients with severe asthma were defined by American Thoracic Society criteria. We compared the suppression of LPS-induced cytokine release (monocyte chemotactic protein-1 [MCP-1], macrophage inflammatory protein [MIP] 1alpha, RANTES, tumor necrosis factor alpha, interleukin 1beta (IL-1beta), IL-8, IFN-gamma, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) by dexamethasone from PBMCs of patients with severe asthma (n = 16), patients with nonsevere asthma (n = 19), and normal volunteers (n = 10).Results: There was no difference in baseline spontaneous or stimulated release of these cytokines among groups. LPS-induced release of 10 cytokines was less suppressed by dexamethasone (10(-6) M) in patients with severe asthma compared with patients with nonsevere asthma, with statistical significance achieved for IL-1beta (p < 0.03), IL-8 (p < 0.03), and MIP-1alpha (p < 0.003), and borderline significance for IL-6 (p = 0.054). There was less difference between the two groups for dexamethasone at 10(-8) M. Nuclear histone deacetylase (HDAC) and histone acetyltransferase activities were reduced in patients with severe asthma compared with patients with nonsevere asthma (p < 0.01). HDAC activity reduction correlated directly to the degree of steroid insensitivity of GM-CSF (r = 0.57, p < 0.01) and IFN-gamma (r = 0.56, p < 0.05) release. Reduction in histone acetyltransferase activity related to corticosteroid use rather than asthma severity.Conclusions: Patients with severe asthma have diminished corticosteroid sensitivity of PBMCs when compared with patients with nonsevere asthma, associated with a reduction in HDAC activity that parallels the impaired corticosteroid sensitivity. [ABSTRACT FROM AUTHOR]

Rationale: Increased oxidative stress and decreased superoxide dismutase (SOD) activity in the asthmatic airway are correlated to airflow limitation and hyperreactivity. We hypothesized that asthmatic individuals with higher levels of oxidative stress may have greater loss of SOD activity, which would be reflected systemically in loss of circulating SOD activity and clinically by development of severe asthma and/or worsening airflow limitation.Methods: To investigate this, serum SOD activity and proteins, the glutathione peroxidase/glutathione antioxidant system, and oxidatively modified amino acids were measured in subjects with asthma and healthy control subjects.Results: SOD activity, but not Mn-SOD or Cu,Zn-SOD protein, was lower in asthmatic serum as compared with control, and activity loss was significantly related to airflow limitation. Further, serum SOD activity demonstrated an inverse correlation with circulating levels of 3-bromotyrosine, a posttranslational modification of proteins produced by the eosinophil peroxidase system of eosinophils. Exposure of purified Cu,Zn-SOD to physiologically relevant levels of eosinophil peroxidase-generated reactive brominating species, reactive nitrogen species, or tyrosyl radicals in vitro confirmed that eosinophil-derived oxidative pathways promote enzyme inactivation.Conclusion: These findings are consistent with greater oxidant stress in asthma leading to greater inactivation of SOD, which likely amplifies inflammation and progressive airflow obstruction. [ABSTRACT FROM AUTHOR]

Transient receptor potential vanniloid-1 (TRPV-1) mediates the cough response induced by the pepper extract capsaicin and is expressed in sensory nerves that innervate the airway wall. We determined the expression of TRPV-1 in the airways of patients with chronic persistent cough of diverse causes and with an enhanced capsaicin cough response. We obtained airway mucosal biopsies by fiberoptic bronchoscopy in 29 patients with chronic cough and 16 healthy volunteers without a cough. Immunostaining for nerve profiles with anti--protein gene product (PGP)-9.5 antibody showed no increase in nerve profiles in the airway epithelium of patients with chronic cough; however, with an anti--TRPV-1 antibody, there was a fivefold increase of TRPV-1 staining nerve profiles (p < 0.001). There was a significant correlation between capsaicin tussive response and the number of TRPV-1--positive nerves within the patients with cough. Our findings indicate that TRPV-1 receptors may contribute to an enhanced cough reflex and the cough response in chronic persistent cough of diverse causes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a study by M. Nikpour et al which noted the lack of Australian epidemiological data for lupus treatment.

Atopic eczema, allergic broncho-pulmonary aspergillosis, helminthic infections and rare primary immunodeficiencies are known to elevate total serum immunoglobulin E ( IgE) above 1000 IU/ mL. However, of 352 patients with IgE >1000 IU/ mL seen in our hospital over a 5-year period, less than 50% had these conditions. Markedly elevated IgE levels in the rest of the patients were associated with asthma, allergic rhinitis and food allergy, instances where the test is of limited diagnostic utility. [ABSTRACT FROM AUTHOR]

A response by the author of the article "Chest ultrasound in practice: a review of utility in the clinical setting," in the April 2012 issue is presented.

In patients with chronic idiopathic cough, there is a chronic inflammatory response together with evidence of airway wall remodelling and an increase in airway epithelial nerves expressing TRPV-1. We hypothesised that these changes could result from an increase in growth factors such as TGFbeta and neurotrophins. We recruited 13 patients with persistent non-asthmatic cough despite specific treatment of associated primary cause(s), or without associated primary cause, and 19 normal non-coughing volunteers without cough as controls, who underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies. There was a significant increase in the levels of TGFbeta in BAL fluid, but not of nerve growth factor(NGF) and brain-derived nerve growth factor(BDNF) compared to normal volunteers. Levels of TFGbeta gene and protein expression were assessed in bronchial biopsies. mRNA expression for TGFbeta was observed in laser-captured airway smooth muscle and epithelial cells, and protein expression by immunohistochemistry was increased in ASM cells in chronic cough patients, associated with an increase in nuclear expression of the transcription factor, smad 2/3. Subbasement membrane thickness was significantly higher in cough patients compared to normal subjects and there was a positive correlation between TGF-beta levels in BAL and basement membrane thickening. TGFbeta in the airways may be important in the airway remodelling changes observed in chronic idiopathic cough patients, that could in turn lead to activation of the cough reflex. [ABSTRACT FROM AUTHOR]