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BACKGROUND AND OBJECTIVE Caring for people with severe asthma and chronic obstructive pulmonary disease (COPD) can impair the quality of life (QoL) of the carer. We aimed to describe the QoL and needs of severe asthma and COPD carers. METHODS Carers of severe asthma (n = 89) and COPD (n = 48) completed an online cross-sectional survey assessing QoL and carer support needs using the Short Form Health Survey 12v2 (SF-12), the Hospital Anxiety and Depression Scale (HADS) and Carers Support Needs Assessment Tool (CSNAT) questionnaires. RESULTS Carers of people with severe asthma and COPD were similar in age (mean ± SD 57.78 ± 14.09 vs. 56.93 ± 12.91) and gender (65% female vs. 66%); however, they differed in caring duration (proportion caring for >10 years: 65% vs. 33%, p

Oral corticosteroids (OCS) are frequently used for asthma treatment. This medication is highly effective for both acute and chronic diseases, but evidence indicates that indiscriminate OCS use is common, posing a risk of serious side effects and irreversible harm. There is now an urgent need to introduce OCS stewardship approaches, akin to successful initiatives that optimized appropriate antibiotic usage. The aim of this TSANZ (Thoracic Society of Australia and New Zealand) position paper is to review current knowledge pertaining to OCS use in asthma and then delineate principles of OCS stewardship. Recent evidence indicates overuse and over-reliance on OCS for asthma and that doses >1000 mg prednisolone-equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS-related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add-on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk–benefits of OCS medications, side effects, effective add-on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.

BACKGROUND AND OBJECTIVE The aim of this secondary analysis of a randomized controlled trial (RCT) of asthma management in pregnancy was to determine the treatment decision differences between a symptom control algorithm and a fractional exhaled nitric oxide (FENO)-guided algorithm, and whether the approach was effective in non-eosinophilic asthma (NEA). METHODS In this double-blind parallel group RCT, women with asthma were randomized prior to 22 weeks gestation to treatment adjustment according to a symptom control algorithm (control group), or a FENO-guided algorithm (inhaled corticosteroid (ICS) dose adjusted according to FENO with long-acting beta-agonist (LABA) added for uncontrolled symptoms). NEA was classified as baseline blood eosinophils

Background and objective: Physical activity (PA) in obstructive airway diseases (OAD) is likely to be impaired but this has not been extensively studied outside of chronic obstructive pulmonary disease (COPD). We describe PA levels in severe asthma and bronchiectasis compared to moderate–severe COPD and to controls, and tested the cross-sectional associations of PA (steps/day) with shared disease characteristics in the OAD group. Methods: Adults with OAD (severe asthma = 62, COPD = 67, bronchiectasis = 60) and controls (n = 63) underwent a multidimensional assessment, including device-measured PA levels. Results: The OAD group included 189 participants (58.7% females), with median (interquartile range) age of 67 (58–72) years and mean forced expiratory volume in the first second (FEV) % predicted of 69.4%. Demographic characteristics differed between groups. Compared to controls (52.4% females, aged 55 (34–64) years, median 7640 steps/day), those with severe asthma, bronchiectasis and COPD accumulated less steps/day: median difference of −2255, −2289, and −4782, respectively (P ≤ 0.001). Compared to COPD, severe asthma and bronchiectasis participants accumulated more steps/day: median difference of 2375 and 2341, respectively (P ≤ 0.001). No significant differences were found between the severe asthma and bronchiectasis group. Exercise capacity, FEV% predicted, dyspnoea and systemic inflammation differed between groups, but were each significantly associated with steps/day in OAD. In the multivariable model adjusted for all disease characteristics, exercise capacity and FEV% predicted remained significantly associated. Conclusion: PA impairment is common in OAD. The activity level was associated with shared characteristics of these diseases. Interventions to improve PA should be multifactorial and consider the level of impairment and the associated characteristics.

The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes.

Asthma is a chronic respiratory disease characterized by respiratory symptoms, airway inflammation, airway obstruction and airway hyper-responsiveness. Asthma is common and directly affects 10% of Australians, 1-5% of adults in Asia and 300 million people worldwide. It is a heterogeneous disorder with many clinical, molecular, biological and pathophysiological phenotypes. Current management strategies successfully treat the majority of patients with asthma who have access to them. However, there is a subset of an estimated 5-10% of patients with asthma who have severe disease and are disproportionately impacted by symptoms, exacerbations and overall illness burden. The care required for this relatively small proportion of patients is also significant and has a major impact on the healthcare system. A number of new therapies that hold promise for severe asthma are currently in clinical trials or are entering the Australian and international market. However, recognition of severe asthma in clinical practice is variable, and there is little consensus on the best models of care or how to integrate emerging and often costly therapies into current practice. In this article, we report on roundtable discussions held with severe asthma experts from around Australia, and make recommendations about approaches for better patient diagnosis and assessment. We assess current models of care for patient management and discuss how approaches may be optimized to improve patient outcomes. Finally, we propose mechanisms to assess new therapies and how to best integrate these approaches into future treatment.

Background and objective Obesity is an established risk factor for poor health outcomes, but paradoxically in chronic obstructive pulmonary disease (COPD), it is associated with improved survival and lung function. A major evidence gap exisits to inform treatment recommendations for patients with COPD who are obese. We aimed to determine the effect of weight reduction involving a low-energy diet utilizing a partial meal replacement plan, coupled with resistance exercise training in obese COPD patients. Methods In a proof of concept before–after clinical trial, obese (body mass index ≥30 kg/m2) COPD patients received a 12 week weight reduction programme involving meal replacements, dietary counselling by a dietitian and resistance exercise training prescribed and supervised by a physiotherapist. Patients were reviewed face to face by the dietitian and physiotherapist every 2 weeks for counselling. Results Twenty-eight participants completed the intervention. Mean (standard deviation) body mass index was 36.3 kg/m2 (4.6) at baseline and reduced by 2.4 kg/m2 ((1.1) P

Background and objective Neutrophil extracellular traps (NETs) are web-like structures comprising DNA and antimicrobial proteins, expelled from neutrophils during NETosis. Persistence of NETs can be pro-inflammatory, yet their role in respiratory disease remains unclear. This study aimed to investigate the presence of NETs in sputum from patients with asthma and COPD, and the relationship of NETs with inflammatory phenotype and disease severity. Methods Induced sputum was collected from healthy controls, asthma and COPD patients. Extracellular DNA (eDNA) was quantified by PicoGreen. LL-37, α-defensins1–3, NE, IL-1β and CXCL8 were quantified by ELISA. PAD4 and NLRP3 gene expression was performed using qPCR. NETs were imaged in sputum smears using immunofluorescence microscopy. Results Sputum eDNA and NET neutrophil antimicrobial proteins were significantly elevated in asthma and COPD compared with healthy controls. Levels of eDNA and NET components were significantly higher in neutrophilic versus non-neutrophilic asthma and COPD. NETs were clearly visualized in sputum smears. PAD4 mRNA was upregulated in neutrophilic COPD. The level of eDNA was higher in severe asthma. High eDNA levels were associated with heightened innate immune responses, including elevated CXCL8 and IL-1β, and NLRP3 gene expression in both COPD and asthma. Antimicrobial proteins and eDNA were positively correlated with airway neutrophils, and negatively correlated with lung function and symptoms. Conclusion NETs are present in the airways of subjects with asthma and COPD. Accumulation of excessive NETs was associated with activation of innate immune responses contributing to disease pathogenesis in chronic airway disease.

Background and objective Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and inflammation. Airway bacterial colonization is increased in COPD; however, the role of potentially pathogenic and non-pathogenic bacteria in the pathogenesis of disease is unclear. This study characterized the presence of bacteria in a well-characterized cohort of adults with COPD and healthy controls. Methods Adults with COPD (n = 70) and healthy controls (n = 51) underwent clinical assessment and sputum induction. Sputum was dispersed, and total and differential cell counts were performed. Bacteria were cultured, identified and enumerated. Supernatants were assessed for neutrophil elastase (NE) and IL-1β. Common respiratory pathogens were also determined using real-time PCR. Results Participants with COPD had a typical neutrophilic inflammatory profile. The total load of bacteria was increased in COPD and was associated with poorer respiratory health status, as measured by the St George's Respiratory Questionnaire (Spearman's r = 0.336, P = 0.013). Significantly lower levels of culturable Bacillus species were identified compared with healthy controls. PCR analyses revealed increased rates of detection of potentially pathogenic bacteria with Haemophilus influenzae detection associated with higher sputum levels of NE and IL-1β, while Streptococcus pneumoniae was more common in male ex-smokers with emphysema and a deficit in diffusion capacity. Conclusion Non-pathogenic and pathogenic bacteria were altered in the sputum of patients with COPD. These observations highlight the potential to identify treatment and management strategies that both target specific bacterial pathogens and restore the microbial balance, which may lead to reductions in inflammation and subsequent improvements in lung health.

Background and objective Neutrophilic inflammation has been implicated in non-eosinophilic asthma (NEA) in adults, but little is known about NEA in children/adolescents. We assessed clinical and inflammatory characteristics of NEA in adolescent asthma. Methods Airway inflammation, sputum endotoxin, airway hyper-reactivity, atopy and lung function were assessed in 77 adolescents with asthma and 68 without asthma (12–17 years). Asthma was identified on the basis of wheeze and asthma history. Results The proportion of NEA (sputum eosinophils

Chronic obstructive pulmonary disease (COPD) frequently coexists with other conditions often known as comorbidities. The prevalence of most of the common comorbid conditions that accompany COPD has been widely reported. It is also recognized that comorbidities have significant health and economic consequences. Nevertheless, there is scant research examining how comorbidities should be assessed and managed in the context of COPD. Also, the underlying mechanisms linking COPD with its comorbidities are still not fully understood. Owing to these knowledge gaps, current disease-specific approaches provide clinicians with little guidance in terms of managing comorbid conditions in the clinical care of multi-diseased COPD patients. This review discusses the concepts of comorbidity and multi-morbidity in COPD in relation to the overall clinical outcome of COPD management. It also summarizes some of the currently available clinical scores used to measure comorbid conditions and their prognostic abilities. Furthermore, recent developments in the proposed mechanisms linking COPD with its comorbidities are discussed.

Background and objective While weight loss has been shown to reduce obesity-related comorbidity, many weight loss treatments fail. Factors that enhance weight loss success are unknown, particularly in those with asthma. The aim of the study was to identify patient characteristics that predict weight loss success in adults with asthma. Methods Baseline and change in asthma characteristics and eating behaviours were investigated for relationships with weight loss and fat loss using multiple linear regression, in 38 overweight and obese adults with asthma randomized to dietary, exercise or combined interventions targeting weight loss for 10 weeks. Results Mean ± standard deviation weight loss was 6.6 ± 5.1 kg. Greater %weight loss and %fat loss was achieved in those with poorer asthma-related quality of life at baseline ((r = 0.398, P = 0.015) and (r = 0.455, P = 0.005) respectively), with 1.7% greater absolute weight loss at week 10 corresponding to each one unit reduction in the asthma-related quality of life score at baseline. Furthermore, a lower baseline forced expiratory volume in 1 s/forced vital capacity correlated with greater weight loss (r = 0.398, P = 0.015). Male sex was associated with a 3.6 kg greater weight loss (P = 0.087). Reducing emotional eating during the programme was associated with greater weight loss in women (r = 0.576, P = 0.010). Conclusions This study demonstrates that individuals with more severe asthma at baseline are more successful in achieving weight loss, which could be a consequence of greater motivation and could be used as a motivational tool within the clinical setting. Gender tailoring of weight loss programmes may be useful to enhance weight loss success. Future studies are urgently needed to establish predictors of long-term weight loss maintenance in those with asthma. See Editorial, page 179 This study is the first to demonstrate that more severe asthma at baseline, male sex, and improvements in eating behaviours during weight loss are associated with greater weight loss success in overweight and obese adults with asthma. Our findings may inform the development of asthma-specific weight management guidelines.

Severe or therapy-resistant asthma represents a major problem, and despite advanced treatment, many patients require oral corticosteroids (OCS). We aimed to determine if patients with severe asthma and elevated peripheral blood eosinophils (PBE) could have treatment with OCS adjusted using an algorithm that controlled PBE (

Background and objectiveThe non-eosinophilic phenotype of asthma (NEA) is associated with chronic airway inflammation and airway neutrophilia. An accumulation of apoptotic airway epithelial cells, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, with the potential for inflammation of surrounding tissues. Apoptosis may occur via the T cell granzyme B pathway. The role of granzyme B in NEA is not known. The aim of this study was to investigate production of granzyme B and its inhibitor proteinase inhibitor (PI)-9 by T cells from induced sputum and compare expression between eosinophilic, NEA and healthy controls.

Background and objective Diseases associated with laryngeal dysfunction include chronic refractory cough (CRC), paradoxical vocal fold movement (PVFM), muscle tension dysphonia (MTD) and globus pharyngeus. We hypothesized the presence of a common sensory laryngeal dysfunction, the ‘laryngeal hypersensitivity’ syndrome, in these conditions. The aim of the study was to compare symptoms and sensory function in patients with CRC, PVFM, MTD and globus. Methods The 103 participants included healthy controls (n = 13) and four case groups: CRC (n = 33), PVFM (n = 28), globus pharyngeus (n = 11) and MTD (n = 18). Participants completed self-report questionnaires: Symptom Frequency and Severity Scale, Voice Handicap Index and the Laryngeal Paraesthesia Questionnaire; and quantitative sensory testing: capsaicin cough reflex sensitivity, hypertonic saline challenge, the timed swallow test, acoustic voice testing, cough frequency monitor and a voice stress test. Results All case groups reported a high-symptom burden in comparison to controls. The case groups showed a similar pattern of symptoms, with impairment in each of the cough, respiration, vocal and upper airway symptom domains. Objective testing revealed significant sensory impairment in the case groups compared to controls and also showed an overlap in sensory dysfunction between the four case groups. Furthermore, there was cross-sensory stimulation of symptoms whereby stimulation of a particular response resulted in symptoms in another domain. Conclusions These discrete clinical laryngeal syndromes display considerable overlap in their clinical features and a common sensory dysfunction, supporting the ‘laryngeal hypersensitivity’ hypothesis. Reconceptualizing functional laryngeal disorders as a form of laryngeal hypersensitivity syndrome provides an alternative approach to management of these perplexing conditions.

Background and objective Increased sputum neutrophilia has been observed in asthma, but also during normal ageing in asthmatics and non-asthmatics. It remains unclear what constitutes ‘normal’ neutrophil levels in different age groups. Methods We assessed the relationship between age and airway neutrophils of 194 asthmatics and 243 non-asthmatics (age range: 6–80 years). Regression analyses were used to assess this relationship adjusted for confounders including asthma status, atopy, gender, smoking and current use of inhaled corticosteroids (ICS). Age-corrected reference values for different age groups were determined using the 95th percentile of non-asthmatic participants. Results Age was positively associated with sputum neutrophils in both asthmatic and non-asthmatic adults (0.46% neutrophil increase/year (95% confidence interval (CI) 0.18, 0.73) and 0.44%/year (0.25, 0.64, respectively), but no association was found in the 95th percentile of non-asthmatic counts for any given age group) were significantly more likely to be asthmatic (odds ratio = 2.5; 95% CI: 1.3, 5.0), with the greatest effect observed in the older age group. Other factors that independently associated with increased sputum neutrophil levels included atopy in non-asthmatic adults, male gender and current use of ICS in asthmatic adults. Age-specific reference values for neutrophil percentage were under 20 years-76%, 20–40 years-62%, 40–60 years-63% and over 60 years-67%. Conclusions Airway neutrophilia is related to age in adults, with a neutrophilic asthma phenotype present in older adults. The use of appropriate age-specific reference values is recommended for future studies aimed at elucidating the role of neutrophils in asthma.

Background & objective Severe asthma exacerbations during pregnancy are a common complication leading to poor health outcomes for both the mother and the baby. Asthma exacerbations are caused most frequently by respiratory viruses. A balance between antiviral and inflammatory immune responses is critical during pregnancy; the balance may be altered by asthma and respiratory virus infection. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from (i) non-pregnant healthy controls, (ii) pregnant non-asthmatics, (iii) post-partum non-asthmatics, (iv) non-pregnant asthmatics (v) pregnant asthmatics, and (vi) post-partum asthmatics. Cells were cultured in vitro with the mitogen phytohaemagglutinin or with a strain of the 2009 pandemic swine influenza. Interferon (IFN)-γ, interleukin (IL)-10 and IL-17 protein were measured from culture supernatant. Neutrophil counts were obtained in samples from pregnant and post-partum women. Results Following the phytohaemagglutinin stimulation of PBMCs, pregnant asthmatics had significantly higher IL-17 and significantly lower IFN-γ responses compared with healthy non-pregnant women. Following infection with influenza, a significant reduction was also observed in IFN-γ and IL-10 production from PBMC of pregnant asthmatics. The IL-17 response to phytohaemagglutinin correlated with the neutrophil percentage. Differences in IFN-γ, IL-10 and IL-17 were found to persist for at least 6 months post-partum. Conclusions A reduction in antiviral and regulatory immunity with increased inflammation during pregnancy occurs in PBMC from pregnant women with asthma. This novel information may relate to the increased susceptibility and disease severity to respiratory virus infections observed during pregnancy.

Background and objective Dietary intake is an important modifiable risk factor for asthma and may be related to disease severity and inflammation, through the effects of intake of anti-oxidant-rich foods and pro-inflammatory nutrients. This study aimed to examine dietary intake in asthma in relation to asthma severity, lung function, inhaled corticosteroid use, leptin levels and inflammation. Methods Food frequency questionnaires, spirometry and hypertonic saline challenge were completed by 137 stable asthmatics and 65 healthy controls. Plasma leptin was analysed by immunoassay. Induced sputum differential cell counts were determined. Results Subjects with severe persistent asthma consumed more fat and less fibre as compared with healthy controls (odds ratio 1.04 (95% confidence interval: 1.01–1.07), P = 0.014) (odds ratio 0.94 (95% confidence interval: 0.90–0.99), P = 0.018). Among asthmatics, higher fat and lower fibre intakes were associated with lower forced expiratory volume in 1 s and airway eosinophilia. Leptin levels were increased in both male and female asthmatics as compared with healthy controls. No association existed among asthmatics between corticosteroid use and dietary intake. Conclusions It was found that asthmatics within the subgroup of severe persistent asthma have a different pattern of dietary intake as compared with healthy controls, which was associated with lower lung function and increased airway inflammation.

Background and objective: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains are primarily associated with skin and soft tissue infections; however, they are increasingly causing more invasive infections including severe community-acquired pneumonia. The objective of this study was to describe the clinico-pathological characteristics of community-acquired MRSA pneumonia. Methods: A retrospective analysis of case records from January 2002 to August 2008 was performed on patients admitted with community-acquired MRSA pneumonia to two large teaching hospitals. Results: Sixteen patients with community-acquired MRSA pneumonia were identified. Their age ranged from 11 months to 86 years (median age; 30 years). Duration of symptoms before hospital presentation ranged from one to 21 days. Most patients had productive cough, fever and dyspnoea. The most common radiological presentation included multilobar consolidation (8/16), necrotizing consolidation (7/16) and empyema (5/16). Seven patients required intensive care support; four required ionotropic support and five required mechanical ventilation for a mean duration of 53 h and 6.6 days, respectively. Six patients underwent surgery (VATS or open thoracotomy). There was a mean delay of approximately 69 h (range; 18 h to 11 days) after presentation before appropriate MRSA antimicrobial treatment was initiated. Three patients died of complications from pneumonia, all within 72 h of presentation. Among survivors, the average length of hospital stay was 23.8 days (range; 10-49 days). Majority of survivors were left with mild residual radiological changes. Conclusions: Community-acquired MRSA pneumonia is increasing and should be suspected in patients with severe community-acquired pneumonia. There was a delay in initiation of appropriate antimicrobial treatment that could have lead to increased morbidity. We describe the clinico-pathological characteristics of community-acquired methicillin-resistant Staphylococcus aureus pneumonia and report the emergence of community-associated methicillin-resistant S. aureus in Australia as a cause of community-acquired pneumonia resulting in severe morbidity and mortality in otherwise healthy persons.

Severe asthma affects 5-20% of the asthma population but is discordantly responsible for the major burden of illness and impairment to quality of life. Patients with severe asthma continue to experience ongoing symptoms despite maximal therapy. A severe asthma service provides a systematic approach to the management of the disease and aids in confirming the correct diagnosis, managing comorbid conditions that may mimic or aggravate asthma, and provides the environment to optimize treatment and asthma self-management skills and education. A severe asthma service is also the ideal environment for trialling add-on therapies and hence can improve patient outcomes and clinical practice. Within such a service there are many opportunities for training and research. In this article we describe the purpose of a severe asthma clinic, the necessary components of a service including staffing and facilities and the processes for trialling additional therapies used in the management of severe asthma.

Background and objective: Viral nucleic acid may be detected for up to 6 months after an acute asthma deterioration, but the pattern and consequences of viral persistence after acute asthma are incompletely understood. This study investigates the frequency of viral persistence after acute asthma, assesses viral infectivity and determines the host inflammatory responses to viral persistence. Methods: Adults and children presenting to hospital with acute asthma and a confirmed respiratory virus infection were studied acutely and at recovery 4–6 weeks later by clinical evaluation and induced sputum for viral and inflammatory mediator detection. Results: Viral RNA was detected during both acute asthma and recovery visits in 17 subjects (viral persistence), whereas in 22 subjects viral RNA had cleared by recovery (viral clearance). The following viruses were detected at recovery: human rhinovirus: 16; respiratory syncytial virus: 2; influenza: 2. In subjects with viral persistence, eight isolates were different to the virus detected at Visit 1. Forty-four per cent of the human rhinovirus isolates were infective at recovery. Asthma and infection severity were similar in the viral clearance and viral persistence groups. Viral persistence was associated with elevated IL-10 mRNA and inducible protein-10 gene expression. Conclusions: Respiratory viral detection after acute asthma is common, and most often persistence is with non-infective human rhinovirus. There is a host inflammatory response with an altered cytokine environment, and the viral RNA can be source of persistent infection. These effects may have longer-term consequences in asthma.

Background and objective: Infection with rhinovirus (RV) is the most common trigger for acute asthma and COPD. The aim of this study was to characterize the variability in the response of primary bronchial epithelial cells to infection with several strains of RV. Methods: RV strains, RV-43, RV-48 (major group RV), RV-47 (minor) and EV-68 (enterovirus), were cultured from subjects with acute asthma and compared with the laboratory RV strains, RV-16, RV-14 (major) and RV-1B (minor). Primary bronchial epithelial cells were obtained from healthy control and asthmatic subjects by endobronchial brushing. Response to infection was assessed by the release of IL-6, interferon (IFN)-γ induced protein (IP)-10 and IFN-β, as measured by ELISA. Viral replication was assessed by serial titration assays and cell viability by flow cytometry. Results: Major group RV strains and EV-68 all efficiently infected and replicated in epithelial cells causing little cell death. The clinical major group RV strains caused greater release of IL-6 and IP-10 compared with laboratory major group RV strains. Infection with minor group RV resulted in greater release of IP-10, IL-6 and IFN-β that was associated with induction of apoptosis and less efficient viral replication. Asthmatic bronchial epithelial cells were less able to respond by releasing IFN-β following infection with RV-1B. Conclusions: Considerable diversity exists in the response to RV strains, especially between minor and major group RV. The impaired IFN-β response in asthmatic bronchial epithelial cells may make them particularly susceptible to minor group RV.

Objective and background: The course of asthma may be altered during pregnancy with at least one-third of women experiencing a worsening of asthma and 20% having an exacerbation during pregnancy. This study used the novel proteomic technique, surface-enhanced laser desorption ionization-time of flight mass spectrometry to determine if the presence of asthma during pregnancy was associated with alterations in plasma proteins. Methods: Plasma collected from healthy (n = 23) and asthmatic (n = 27) pregnant women at 18 and 30 weeks gestation was applied to strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu) chips. Mass analysis was conducted using Ciphergen Protein Biology System IIc and significant differences in individual peak intensities between groups determined. Results: At 18 weeks gestation, 91 peaks were significantly different between pregnant women with and without asthma, representing 28% of the total peaks identified. At 30 weeks gestation, 51 peaks were significantly different. There were two peaks that were significantly different between groups at both 18 and 30 weeks gestation and expressed at a similar level at both time points. One was increased in asthmatics (MW = 6444 Da) whereas the other decreased in asthmatics compared with non-asthmatic women (MW = 1846 Da). Conclusions: This study demonstrated that there are differences in protein patterns between pregnant women with and without asthma. Other techniques are needed to define the molecular species and classify pathophysiological significance. Surface-enhanced laser desorption ionization-time of flight mass spectrometry has potential as a tool to monitor disease progression in situations such as pregnancy.

Objective: To evaluate induced sputum eosinophils in asthma and chronic cough. Design: This was an analytical, cross-sectional study set in an ambulatory respiratory clinic. Subjects: Subjects (n = 75) referred for evaluation of symptomatic asthma or episodic respiratory symptoms had a clinical assessment, spirometry, hypertonic saline challenge and induced sputum. Two diagnostic groups were identified. The first group comprised subjects with symptomatic asthma and variable airway obstruction (VAO) (n = 32). The second group included subjects with episodic respiratory symptoms and no VAO (n = 43). Results: The prevalence of eosinophilic bronchitis (eosinophils > 2.75%) was greatest in asthma (n = 14, 44%), compared to the episodic respiratory symptoms group (n = 9, 21%, P = 0.02). Clinical variables did not predict increased eosinophils (P > 0.05). Sputum eosinophils were highest in asthmatics not using inhaled corticosteroids (6.5%vs 0.5%, P = 0.02). Sputum neutrophils were higher in subjects using inhaled corticosteroid (53%vs 25%, P = 0.04). Conclusion: Airway inflammation with eosinophilia was common among patients presenting to a respiratory clinic, especially those with asthma who were not using inhaled corticosteroids. Induced sputum also identified eosinophilic bronchitis in those without asthma. It was not possible to detect the presence or absence of airway eosinophilia by routine clinical assessment. The results in this study imply that the assessment of induced sputum eosinophils may be a useful guide to therapy, especially in the assessment of persistent symptoms in asthmatics on corticosteroids, and in the assessment of non-asthmatic subjects with symptoms.

Background and objective Asthma-related morbidity is greater in older compared with younger asthmatics. Airway closure is also greater in older asthmatics, an observation that may be explained by differences in airway inflammation. We hypothesized that in older adult patients with asthma, neutrophil airway inflammation increases airway closure during bronchoconstriction, while eosinophil airway inflammation increases airway hyperresponsiveness (AHR). Methods Asthmatic subjects (n = 26), aged ≥55 years (68% female), were studied, and AHR to 4.5% saline challenge was measured by the response–dose ratio (%fall in forced expiratory volume in 1 s (FEV1)/mg saline). Airway closure was assessed during bronchoconstriction percent change in forced vital capacity (FVC)/percent change in FEV1 (i.e. Closing Index). Airway inflammation was assessed by induced sputum and exhaled nitric oxide (eNO). Results Mean patient age was 67 years (confidence interval: 63–71) with a mean FEV1 of 78 % predicted (confidence interval: 70–85%). AHR correlated with sputum eosinophils (r = 0.68, P = 0.005) and eNO (r = 0.71, P