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Background Asthma epidemics associated with thunderstorms have had catastrophic impacts on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population. Objective We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR. Methods This multi-centre study recruited adults from Melbourne (Australia) with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry, white blood-cell count, ryegrass pollen specific IgE (RGP-spIgE) and fractional exhaled nitric oxide (FeNO) were measured to identify risk factors for a history of TA in individuals with SAR. Results From a total of 228 individuals with SAR, 35% (80/228) reported SAR only (I-SAR), 37% (84/228) reported TA symptoms but had not attended hospital for treatment (O-TA) and 28% (64/228) had presented to hospital for TA (H-TA). All H-TA patients reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower forced expiratory volume in one second (FEV1) and asthma control questionnaire (ACQ) score >1.5 were associated with H-TA. Higher blood RGP-spIgE, eosinophil counts, and FeNO were significantly associated with both O-TA and H-TA. Receiver-operating curve (ROC) analysis showed RGP-spIgE >10·1 kU/L and pre-bronchodilator FEV1 ≤90% to be biomarkers of increased H-TA risk. Conclusion Clinical tests can identify risk for a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations.

Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities is needed to inform clinical practice.To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA.Patients enrolled in the Australian Mepolizumab Registry (n=309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin exacerbated airway disease, asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO), fungal sensitisation and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed.Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range 47-77%), maintenance oral corticosteroid use (dose reduction 4.2-13.3 mg/day), and improved symptom control (Asthma Control Questionnaire-5 score 1.9-2.4 point reduction) and lung function (mean 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1s). Peripheral blood eosinophils were reduced (mean 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO and fungal sensitisation) modified the baseline phenotype.Mepolizumab treatment is associated with comparable clinical improvements in in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

Many patients with difficult asthma also have coexisting vocal cord dysfunction (VCD), evident by paradoxical vocal fold motion (PVFM) on laryngoscopy.Among patients with difficult asthma, we sought to identify clinical features associated with laryngoscopy-diagnosed PVFM.Consecutive patients with "difficult asthma" referred by respiratory specialists underwent systematic assessment in this observational study. Those with a high clinical suspicion for VCD were referred for laryngoscopy, either at rest or after mannitol provocation. Statistical analyses were performed to identify clinical factors associated with PVFM, and a multivariate logistic regression model was fitted to control for confounders.Of 169 patients with difficult asthma, 63 (37.3%) had a high clinical probability of VCD. Of 42 who underwent laryngoscopy, 32 had PVFM confirmed. Patients with PVFM more likely had preserved lung function (prebronchodilator forced expiratory ratio 74% ± 11 vs 62% ± 16, P.001); physiotherapist-confirmed dysfunctional breathing (odds ratio [OR] = 5.52, 95% confidence interval [CI]: 2.4-12.7, P.001), gastro-oesophageal reflux (OR = 2.6, 95% CI: 1.16-5.8, P = .02), and a lower peripheral eosinophil count (0.09 vs 0.23, P = .004). On multivariate logistic regression, independent predictors for PVFM were dysfunctional breathing (OR = 4.93, 95% CI: 2-12, P.001) and preserved lung function (OR = 1.07, 95% CI: 1.028-1.106, P.001).Among specialist-referred patients with difficult asthma, VCD pathogenesis may overlap with dysfunctional breathing but is not associated with severe airflow obstruction. Dysfunctional breathing and preserved lung function may serve as clinical clues for the presence of VCD.

Background Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition. Objective To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR. Methods The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members. Results Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV1. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed. Conclusions This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs.

Background Understanding of dysfunctional breathing in patients with difficult asthma who remain symptomatic despite maximal inhaler therapy is limited. Objective We characterized the pattern of dysfunctional breathing in patients with difficult asthma and identified possible contributory factors. Methods Dysfunctional breathing was identified in patients with difficult asthma using the Nijmegen Questionnaire (score >23). Demographic characteristics, asthma variables, and comorbidities were assessed. Multivariate logistic regression was performed for dysfunctional breathing, adjusted for age, sex, body mass index, and airflow obstruction. Results Of 157 patients with difficult asthma, 73 (47%) had dysfunctional breathing. Compared with patients without dysfunctional breathing, those with dysfunctional breathing experienced poorer asthma status (symptom control, quality of life, and exacerbation rates) and greater unemployment. In addition, more frequently they had elevated sino-nasal outcome test scores, anxiety, depression, sleep apnea, and gastroesophageal reflux. On multivariate analysis, anxiety (odds ratio [OR], 3.26; 95% CI, 1.18-9.01; P = .02), depression (OR, 2.8; 95% CI, 1.14-6.9; P = .03), and 22-item sino-nasal outcome test score (OR, 1.03; 95% CI, 1.003-1.05; P = .03) were independent risk factors for dysfunctional breathing. Conclusions Dysfunctional breathing is common in difficult asthma and associated with worse asthma status and unemployment. The independent association with psychological disorders and nasal obstruction highlight an important interaction between comorbid treatable traits in difficult asthma.

Work‐related asthma (WRA) is one of the most common occupational respiratory conditions, and includes asthma specifically caused by occupational exposures (OA) and asthma that is worsened by conditions at work (WEA). WRA should be considered in all adults with asthma, but especially those with new‐onset or difficult to control asthma. Improvement in asthma symptoms when away from work is suggestive of WRA. Clinical history alone is insufficient to diagnose WRA; therefore, objective investigations are required to confirm the presence of asthma and the association of asthma with work activities. Management of WRA requires pharmacotherapy similar to that of non‐WRA, however, also needs to take into account control of the causative workplace exposure. Ongoing exposure will likely lead to decline in lung function and worsening asthma control. WRA is a preventable condition but this does rely on increased awareness of WRA and thorough identification and control of all potential occupational respiratory hazards.

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL−1. Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); pMepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.

Oral corticosteroids (OCS) carry serious health risks. Innovative treatment options are required to reduce excessive exposure and promote OCS stewardship.This study evaluated the trajectories of OCS exposure (prednisolone-equivalent) in patients with severe eosinophilic asthma before and after starting mepolizumab and the predictors of becoming OCS free after 6 months of mepolizumab therapy.This real-world observational study included 309 patients from the Australian Mepolizumab Registry who were followed up for 1 year (n = 225).Patients had a median age of 60 (interquartile range: 50, 68) years, and 58% were female. At baseline, 48% used maintenance OCS, 96% had ≥1 OCS burst, and 68% had received ≥1 g of OCS in the previous year. After commencing mepolizumab, only 55% of those initially on maintenance OCS remained on this treatment by 12 months. Maintenance OCS dose reduced from median 10 (5.0, 12.5) mg/day at baseline to 2 (0, 7.0) mg/day at 12 months (P.001). Likewise, proportions of patients receiving OCS bursts in the previous year reduced from 96% at baseline to 50% at 12 months (P.001). Overall, 137 (48%) patients required OCS (maintenance/burst) after 6 months' mepolizumab therapy. Becoming OCS free was predicted by a lower body mass index (odds ratio: 0.925; 95% confidence interval: 0.872-0.981), late-onset asthma (1.027; 1.006-1.048), a lower Asthma Control Test score (1.111; 0.011-1.220), and not receiving maintenance OCS therapy at baseline (0.095; 0.040-0.227).Mepolizumab led to a significant and sustained reduction in OCS dependence in patients with severe eosinophilic asthma. This study supports the OCS-sparing effect of mepolizumab and highlights the pivotal role of mepolizumab in OCS stewardship initiatives.

Guidelines endorse systematic assessment for severe asthma, with data indicating benefit across multiple outcome domains.We examined which patients respond to systematic assessment and whether oral corticosteroid burden can be decreased independent of monoclonal biologic use.Specialist-referred patients are assessed systematically for difficult asthma at our center. We undertook a responder analysis for improvements in the domains of symptom control, quality of life, exacerbations, and airflow obstruction, assessed 6 months after initial assessment. Multivariate analyses were performed for each domain to identify predictors of response. Changes in oral corticosteroid burden were also measured, stratified by monoclonal biologics commenced during assessment.Among 161 patients assessed systematically, 64% had a reduction in exacerbations, 54% achieved minimum clinically important differences for both symptom control and quality of life, and 40% increased their forced expiratory volume in 1 second by ≥100 mL. Altogether, 87% of patients with asthma improved in at least 1 domain. The most consistent predictor of response across domains was poorer baseline asthma status. There was a substantial reduction in mean chronic oral corticosteroid dose (11-5 mg, n = 46, P.001), even after excluding 7 patients commenced on monoclonal biologics (11-5.6 mg, n = 39, P.001).Almost 90% of patients undergoing systematic assessment for difficult asthma improve significantly in at least 1 key asthma outcome, with few reliable predictors of response. The halving of oral corticosteroid burden during systematic assessment is independent of, and comparable in magnitude with, that achieved by monoclonal biologics.

Background: Epidemic thunderstorm asthma (ETSA) severely affected Melbourne, Australia in November 2016. There is scant literature on the natural history of individuals affected by ETSA. Objective: A multicentre 12-month prospective observational study was conducted assessing symptomatology and behaviors of ETSA-affected individuals. Methods: We used a structured phone questionnaire to assess asthma symptom frequency, inhaled preventer use, asthma action plan ownership and healthcare utilization over 12 months since the ETSA. Analysis of results included subgroup analyses of the "current," "past," "probable," and "no asthma" subgroups defined according to their original 2016 survey responses. Results: Four hundred forty-two questionnaires were analyzed. Eighty percent of individuals reported ongoing asthma symptoms at follow-up, of which 28% were affected by asthma symptoms at least once a week. Risk of persistent asthma symptoms was significantly higher in those with prior asthma diagnosis, current asthma, and probable undiagnosed asthma (all p < 0.01). Of 442 respondents, 53% were prescribed inhaled preventers, of which 51% were adherent at least 5 days a week. Forty-two percent had a written asthma action plan and 16% had sought urgent medical attention for asthma in the preceding year. Conclusions: Following an episode of ETSA, patients experience a pivotal change in asthma trajectory with both loss of asthma control and persistence of de novo asthma. Suboptimal rates of inhaled preventer adherence and asthma action plan ownership may contribute to asthma exacerbation risk and susceptibility to future ETSA episodes. Longer-term follow-up is needed to determine the extent and severity of this apparent change.

Severe asthma is complex and heterogeneous; ad hoc outpatient assessment can be suboptimal. Systematic evaluation improves outcomes and is recommended by international guidelines. Electronic templates improve physician performance and clinical processes, and may be useful in severe asthma systematic evaluation. We developed the Severe Asthma Global Evaluation (SAGE) electronic platform to streamline this process, via Research Electronic Data Capture (REDCap). It incorporates: a questionnaire battery for patient completion before clinical consultation; asthma and comorbidity modules; a clinical summary page in an asthma management module; a nurse educator module; a structured panel discussion record; and an automatically generated report incorporating all key data. SAGE incorporates 282 clinician input fields, with a typical consultation requiring completion of 169. To streamline the process SAGE contains 34 autocalculations and 20 decision support tools. It incorporates all 95 core variables of the International Severe Asthma Registry, with which it is directly compatible. SAGE improves symptom control and exacerbations in patients with difficult asthma. In conclusion, we developed and validated an electronic platform that facilitates a comprehensive but streamlined systematic evaluation of severe asthma that is available for free download via REDCap. Its use enhances management of patients with severe asthma and facilitates audit and international research collaboration.

Background and objective Little is known about how comorbidities affect difficult asthma patients across different domains of asthma outcomes. We hypothesized that comorbidities in difficult asthma significantly influence asthma outcomes. Methods We analysed 90 consecutive patients who underwent systematic assessment at our hospital's difficult asthma clinic. Eight comorbidities were assessed in all patients. They were allergic rhinitis, chronic rhinosinusitis (CRS), gastroesophageal reflux disease, obesity, obstructive sleep apnoea, anxiety or depression, dysfunctional breathing (DB) and vocal cord dysfunction (VCD). Asthma outcomes examined were exacerbation frequency (≥3/year vs

Background: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be assessed using registry data, the prevalence of traits in severe and non-severe asthma, and whether particular treatable traits were associated with future exacerbation risk. Methods: The Australasian Severe Asthma Web-based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 with non-severe. Published treatable traits were mapped to registry data fields and their prevalence described. Participants were characterised at baseline and each 6 months for 24 months. Results: In SAWD, 24 treatable traits were identified in three domains: pulmonary (7 traits), extrapulmonary (13 traits) and behavioural/risk-factors (4 traits). People with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitisation, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being exacerbation prone (IRR 2.07 (1.66, 2.58), depression (IRR 1.63 (1.31, 1.88), inhaler-device polypharmacy (IRR 1.51 (1.31, 1.75), vocal cord dysfunction (IRR 1.51 (1.22, 1.88) and obstructive sleep apnoea (IRR 1.41 (1.05, 1.89). Conclusion: Treatable traits can be assessed using severe asthma registry data. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating clinical utility of assessing treatable traits.

Background and objective: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. Methods: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. Results: In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk; among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. Conclusion: Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.

Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood.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.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.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).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.

Bronchoalveolar lavage (BAL) is a commonly used diagnostic and research tool. Currently, there is limited evidence regarding standardizing this technique. The type of suction method and number of aliquots used as well as the anatomic lung segment sampled are not standardized nor well studied. Our primary aim was to compare the quantity and quality of BAL specimens using 2 suction methods, hand-held syringe versus wall suction. Our secondary aim was to assess which anatomic lung segment yields the greatest BAL results and how many aliquots are required.A prospective clinical study was performed in patients undergoing bronchoscopies using hand-held syringe or wall suction. On the basis of radiologic findings, 100 mL (with 4 aliquots) of normal saline was instilled and the percentage volume return calculated.Sixy-six patients were enrolled. Thirty-three patients received hand-held syringe and 33 using wall suction. There was no significant difference in the percentage volume returned, or the adequacy of fluid between these suction methods. When comparing volumes of return from different lobes, greater returns were demonstrated from the right middle lobe (P=0.002). In addition, with each sequential aliquot instilled, the return of fluid was increased significantly (P0.001).No significant difference was observed between hand-held syringe and wall suction in terms of volumes returned and microbiological or diagnostic yield. Performance of BAL in the right middle lobe is associated with increased return and should be preferentially used when performing a nontargeted BAL in patients with diffuse computed tomography chest changes.

Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty. Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking >75% of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period. Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data; including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%). At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies., Preventer adherence is underrecognised and must be confirmed objectively prior to initiating novel asthma treatment http://ow.ly/Kc1X30iysYD

Bioaerosols’ emission from an activated sludge wastewater treatment plant with surface aerators was surveyed from November 2009 to July 2010. Health effects among plant workers were assessed by checklist and through interviews by an internist. Samples were collected by the Anderson sampler in eight days of the year and analyzed for Standard Plate Count, Total Coliforms, Fecal Coliforms, and Fecal Streptococci. It was found that most sewage treatment plant’s staffs were adversely affected as a result of bioaerosols’ inhalation. Major observed health effects were fatigue, dizziness, eye irritation, and abdominal pain. The most common size of bacterial-aerosols was higher than 8.2 μm. Maximum and minimum concentrations of bacterial-aerosols were found in the sludge aerobic digester unit (1,537 CFU/m3) and the secondary settlers (4 CFU/m3), respectively. Average concentrations of bacterial-aerosols were much lower in summer (742 CFU/m3) as compared to winter (3780 CFU/m3). Given the observed adverse ...

Aim We determined the proportion of asthma patients under specialist care who remain difficult-to-treat and might benefit from systematic assessment. We additionally report the characteristics and indications for referral in 90 patients who received systematic assessment for difficult asthma. Methods We conducted a three-month prospective audit of our hospital’s general asthma clinic. We then analyzed consecutive patients over 18 months referred on for systematic assessment of difficult asthma. Results Over 3 months, 22/166 patients (13.3%) in the general asthma clinic were considered likely to benefit from systematic assessment of difficult asthma. These patients had higher inhaled steroid requirements (890 ± 604 mg), lower lung function (FEV1: 65 ± 18%), and more often received GINA step 5 treatment (22.7%). However, 7/22 (32%) of suitable patients were not referred for assessment, mainly due to patient factors. Over 18 months, 90 patients received systematic assessment for difficult asthma, on account of poor symptom control (62%), frequent exacerbations (44%), poor lung function (42%), patient factors (29%), and diagnostic uncertainty (26%). There was a high disease burden with a mean (±SD) asthma control test score and asthma quality of life questionnaire score of 14 ± 5 and 4.26 ± 1.45 respectively. 80% fulfilled criteria for severe asthma. The majority were either atopic (66.7%) or eosinophilic (54.4%); only 15.6% were neither. Patients had a median of three extra-pulmonary comorbidities, of which most were previously unrecognised. Conclusion One-in-eight asthma patients already under specialist care were suitable for systematic assessment of difficult asthma, but a third of these were not referred due to patient factors. Diagnostic uncertainty and patient factors were important indications for systematic assessment. Most patients who underwent systematic assessment exhibited severe asthma phenotypes potentially responsive to targeted treatment, but also had multiple comorbidities. Our results highlight the importance of management strategies to address patient factors, severe asthma biology, and concurrent contributory conditions.

Objective: Multiple extra-pulmonary comorbidities contribute to difficult asthma, but their diagnosis can be challenging and time consuming. Previous data on comorbidity detection have focused on clinical assessment, which may miss certain conditions. We aimed to locate relevant validated screening questionnaires to identify extra-pulmonary comorbidities that contribute to difficult asthma, and evaluate their performance during a difficult asthma evaluation. Methods: MEDLINE was searched to identify key extra-pulmonary comorbidities that contribute to difficult asthma. Screening questionnaires were chosen based on ease of use, presence of a cut-off score, and adequate validation to help systematically identify comorbidities. In a consecutive series of 86 patients referred for systematic evaluation of difficult asthma, questionnaires were administered prior to clinical consultation. Results: Six difficult asthma comorbidities and corresponding screening questionnaires were found: sinonasal disease (allergic rhinitis and chronic rhinosinusitis), vocal cord dysfunction, dysfunctional breathing, obstructive sleep apnea, anxiety and depression, and gastro-oesophageal reflux disease. When the questionnaires were added to the referring clinician's impression, the detection of all six comorbidities was significantly enhanced. The average time for questionnaire administration was approximately 40 minutes. Conclusions: The use of validated screening questionnaires heightens detection of comorbidities in difficult asthma. The availability of data from a battery of questionnaires prior to consultation can save time and allow clinicians to systematically assess difficult asthma patients and to focus on areas of particular concern. Such an approach would ensure that all contributing comorbidities have been addressed before significant treatment escalation is considered.

© 2015 King et al. Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.

Systematic evaluation is advocated for difficult asthma, but how best to deliver such care is unclear and outcome data are scarce.We describe our institution's structured approach to difficult asthma management and report on the outcomes of such an approach.Eighty-two consecutive patients with difficult asthma referred to our clinic from respiratory specialists were evaluated in 3 key areas: diagnostic confirmation, comorbidity detection, and inflammatory phenotyping. We then optimized treatment including relevant comorbidity interventions. The outpatient protocol was supported by comorbidity questionnaires, an electronic clinic template, and standardized panel discussion. Asthma outcomes were assessed at 6 months.Sixty-eight patients completed follow-up. Asthma diagnosis was refuted in 3 patients and the remaining 65 patients were included in the study analysis. There was no overall escalation of inhaled or oral corticosteroids. Patients had a median of 3 comorbidities, and a median of 3 comorbidity interventions. Control of chronic rhinosinusitis and dysfunctional breathing improved among patients with these diagnoses (22-item Sino-Nasal Outcome Test score from 47 ± 20 to 37 ± 22, P = .017; Nijmegen score from 32 ± 6 to 25 ± 9, P = .003). There were overall improvements in the Asthma Control Test score (from 14 ± 5 to 16 ± 6, P.001), the Asthma Quality of Life Questionnaire (from 4.29 ± 1.4 to 4.65 ± 1.5, P = .073), and the frequency of exacerbations over 6 months (from 2 [interquartile range, 0-4] to 0 [interquartile range, 0-2], P.001).In patients referred with difficult asthma from respiratory specialists, a structured approach coupled with targeted comorbidity interventions improved control of key comorbidities and enhanced asthma outcomes.

A healthy 29-year-old Australian man with cystic fibrosis (CF) grew Burkholderia pseudomallei on a routine sputum culture 1 month after returning from holiday in Thailand. He underwent a 12-month treatment regime with multiple antibiotics resulting in a number of adverse events. Sputum cultures were cleared of the pathogen and remain negative 8 years post-treatment. There were no clinical sequelae and no deterioration in lung function. Few reports have been published to date on melioidosis in CF patients. The proposed management for this infection includes multiple antibiotics regimens for prolonged periods of time, which may result in adverse events. Optimal treatment and length of treatment are currently determined on an individual basis.