The perfect storm: temporal analysis of air during the world's most deadly epidemic thunderstorm asthma (ETSA) event in Melbourne.

BACKGROUND: There have been 26 epidemic thunderstorm asthma (ETSA) events worldwide, with Melbourne at the epicentre of ETSA with 7 recorded events, and in 2016 experienced the deadliest ETSA event ever recorded. Health services and emergency departments were overwhelmed with thousands requiring medical care for acute asthma and 10 people died. OBJECTIVES: This multidisciplinary study was conducted across various health and science departments with the aim of improving our collective understanding of the mechanism behind ETSA. DESIGN: This study involved time-resolved analysis of atmospheric sampling of the air for pollen and fungal spores, and intact and ruptured pollen compared with different weather parameters, pollution levels and clinical asthma presentations. METHODS: Time-resolved pollen and fungal spore data collected by Deakin AirWATCH Burwood, underwent 3-h analysis, to better reflect the 'before', 'during' and 'after' ETSA time points, on the days leading up to and following the Melbourne 2016 event. Linear correlations were conducted with atmospheric pollution data provided by the Environment Protection Authority (EPA) of Victoria, weather data sourced from Bureau of Meteorology (BOM) and clinical asthma presentation data from the Victorian Agency for Health Information (VAHI) of Department of Health. RESULTS: Counts of ruptured grass pollen grains increased 250% when the thunderstorm outflow reached Burwood. Increased PM10, high relative humidity, decreased temperature and low ozone concentrations observed in the storm outflow were correlated with increased levels of ruptured grass pollen. In particular, high ozone levels observed 6 h prior to this ETSA event may be a critical early indicator of impending ETSA event, since high ozone levels have been linked to increasing pollen allergen content and reducing pollen integrity, which may in turn contribute to enhanced pollen rupture. CONCLUSION: The findings presented in this article highlight the importance of including ruptured pollen and time-resolved analysis to forecast ETSA events and thus save lives.

RNA sequencing of single allergen-specific memory B cells after grass pollen immunotherapy: Two unique cell fates and CD29 as a biomarker for treatment effect.

BACKGROUND: Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen-specific IgG4 . IgG4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B-cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen-specific Bmem subsets induced by SLIT for grass pollen allergy. METHODS: Blood samples were collected twice outside the pollen season from twenty-seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne) and seasonal rhinoconjunctivitis. Thirteen received 4-month pre-seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single-cell RNA sequencing was performed on FACS-purified Lol p 1-specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort. RESULTS: Four months of SLIT increased RGP-specific IgE and IgG4 in serum and induced two Lol p 1-specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG4 ), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1+ Bmem expressing surface IgG4 , CD23, and CD29 after SLIT. CONCLUSIONS: A clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface-expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.

Epidemic Thunderstorm Asthma: Lessons Learned from the Storm Down-Under.

Epidemic thunderstorm asthma (ETSA) is a global health problem that can strike without sufficient warning and can have catastrophic consequences. Because of climate change, future events are likely to become more common, more disastrous, and more unpredictable. To prevent loss of life and avoid surge events on health care infrastructure, identifying at-risk individuals and their potential biomarkers is the most prophylactic approach that can be taken to mitigate the deadly consequences of ETSA. In this review, we provide an update on the clinical mechanism, global prevalence, and characteristics of those patients moderately or severely at risk of ETSA. Identifying these patient characteristics will aid clinical professionals to provide suitable and personalized treatment plans and, in turn, avoid future loss of life.

12-month randomised controlled trial of ginseng extract for moderate COPD.

BACKGROUND: Panax ginseng (ginseng) is a therapeutic herb which might be beneficial in COPD. The study investigated if ginseng, compared with placebo, is effective and safe for people with moderate COPD. METHODS: This multicentre, randomised, double-blind, placebo-controlled trial compared 24 weeks of ginseng capsules (100 mg twice daily) with placebo. Participants were followed up for a further 24 weeks. Participants were aged 40 years and over and had airflow limitation in the moderate (Global Initiative for Chronic Obstructive Lung Disease 2) COPD range. The coprimary endpoints were the St George's Respiratory Questionnaire, the COPD Assessment Test and the Short Form Health Survey. Secondary outcomes included lung function, exacerbation rate and use of relief medication. FINDINGS: 168 participants were randomised 1:1 from five centres in Australia and China. Baseline characteristics were balanced between groups. There were no significant differences between ginseng and placebo, with overall results improving in both groups. Ginseng seemed safe for, and well tolerated by, people with COPD. INTERPRETATION: There was no significant difference in improvement in health-related quality of life (primary outcome) between the ginseng and placebo groups. TRIAL REGISTRATION NUMBER: ACTRN12610000768099.

Thunderstorm asthma: revealing a hidden at-risk population.

BACKGROUND: Epidemic thunderstorm asthma (ETSA) refers to large-scale acute bronchospasm events associated with thunderstorm. The most serious episode ever recorded occurred in Melbourne, Australia, in November 2016, where more than 3500 patients were treated in hospitals and 10 died. Previous work has been focused primarily on patient presentations to emergency departments. The prevalence of individuals with milder, non-emergent symptoms and who may be at risk of more serious episodes in the future has not previously been explored. AIM: To characterise the nature and extent of respiratory symptoms in healthcare workers during the Melbourne ETSA event. METHODS: A survey was conducted among staff and volunteers across Eastern Health, distributed on the intranet homepage, by email and by word of mouth. Anonymous survey questions were constructed to assess prior and current diagnoses of relevance, symptoms, and demography. RESULTS: There were 515 participants (80% female, n = 411) of approximately 9000 potential respondents (~6% response rate) who completed the survey; 132 (25.6%) had symptoms suggestive of asthma during the Melbourne ETSA event, the majority of whom did not seek professional medical help. Notably, of those with ETSA-like symptoms, only 58 (43.9%) had a history of asthma, while 97 (73.5%) had a history of allergic rhinitis. Specifically, a history of allergic rhinitis (OR 2.77, P < 0.001), a history of asthma (OR 1.67, P = 0.037) and being of self-identified Asian ethnicity (OR 3.24, P < 0.001) were all strong predictors of ETSA-like symptoms. Being predominantly indoors was not protective. CONCLUSIONS: Our study provides evidence of the presence of a large cohort of sufferers during the Melbourne ETSA event of 2016 that did not come to the attention of medical services, implying a potentially hidden and significant susceptible population. Further research should help clarify the true prevalence of vulnerability in the general population, with important public health implications.

The Melbourne epidemic thunderstorm asthma event 2016: an investigation of environmental triggers, effect on health services, and patient risk factors.

BACKGROUND: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies. METHODS: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions. FINDINGS: Grass pollen concentrations on Nov 21, 2016, were extremely high (>100 grains/m3). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died. INTERPRETATION: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma. FUNDING: None.

Ear acupressure for perennial allergic rhinitis: A multicenter randomized controlled trial.

BACKGROUND: Perennial allergic rhinitis (PAR) has a high and increasing prevalence worldwide. Ear acupressure (EAP) is a noninvasive semi-self-administered form of acupuncture. Previous studies indicated that EAP could be effective and safe for AR symptom management. However, there was insufficient evidence to confirm this. This study investigated whether EAP, a noninvasive clinical alternative to acupuncture, is effective and safe for PAR. METHODS: This is an international, multicenter, randomized, single-blind, sham-controlled trial. The trial was conducted at two centers: Royal Melbourne Institute of Technology University (Melbourne, Australia) Clinical Trial Clinic and Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. PAR participants were randomized to receive real or sham EAP treatment once a week for 8 weeks and then were followed-up for 12 weeks. Participants were instructed to administer EAP stimulation three times daily. Symptom severity and quality of life (QoL) were evaluated. Adverse events (AEs) were also monitored. Intention-to-treat analysis on change of symptom scores and QoL was applied. RESULTS: Two hundred forty-five participants were randomly assigned to real (n = 124) and sham EAP (n = 121) groups. Twenty-five participants discontinued during treatment and 15 participants dropped out during follow-up. At the end of treatment and follow-up periods, changes of global QoL score were significantly greater in the real EAP group compared with the sham group. At the end of follow-up, scores for total nasal symptom, runny nose, and eye symptoms in the real EAP group had a greater reduction compared with the sham group. Overall, both real and sham EAP were well tolerated. Two severe AEs were reported but were not considered related to the EAP procedures. CONCLUSION: In conclusion, EAP showed short-term and extended benefit for improving PAR symptoms and QoL for PAR patients.

Panax ginseng therapy for chronic obstructive pulmonary disease: a clinical trial protocol and pilot study.

BACKGROUND: Panax ginseng (Ren shen) has been used to treat chronic obstructive pulmonary disease (COPD). This article aims to present a study protocol and pilot trial comparing P. ginseng with placebo for treating moderate to very severe COPD. METHODS: COPD was diagnosed spirometrically, with participants having a forced expiratory volume in one second (FEV1) of between 20% and 79% and FEV1 to forced vital capacity (FVC) ratio of less than 70%. Outcome measures included exacerbation rate, St. Georges Respiratory Questionnaire, COPD Assessment Test and Short-form Health Survey (SF-36). Other outcome measures included the six-minute walk test, FEV1, FVC, relief medication use, use of COPD-specific medical resources, and adverse events. The study is a randomized, double-blind, placebo controlled clinical trial. The method of this pilot trial was based on a planned full-scale trial except that participants were enrolled for ten weeks compared to 52 weeks. In the pilot trial, 14 participants (57-73 years old) with moderate to very severe COPD were recruited from a community health program at a public Chinese medicine hospital in Guangdong Province, China. After a 2-week run-in period, 10 participants were eligible for the study and were randomly assigned to either P. ginseng group (n = 5) (200 mg twice daily for four weeks) or placebo group (n = 5), and then followed-up for an additional 4 weeks for a total of 10 weeks. RESULTS: Nine participants completed the trial and one dropped out. The exacerbation rate could not be evaluated because there were no exacerbations. One participant in P. ginseng group reported events of sore throat, cough and fever. Trial investigators did not consider these events as COPD exacerbations or adverse events. CONCLUSIONS: Participant recruitment, study design, data collection and outcome measurement have been tested in a pilot trial. A full-scale trial is warranted.

Systematic review of the effectiveness of breathing retraining in asthma management.

In asthma management, complementary and alternative medicine is enjoying a growing popularity worldwide. This review synthesizes the literature on complementary and alternative medicine techniques that utilize breathing retraining as their primary component and compares evidence from controlled trials with before-and-after trials. Medline, PubMed, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library electronic databases were searched. Reference lists of all publications were manually checked to identify studies not found through electronic searching. The selection criteria were met by 41 articles. Most randomized controlled trials (RCTs) of the Buteyko breathing technique demonstrated a significant decrease in ß(2)-agonist use while several found improvement in quality of life or decrease in inhaled corticosteroid use. Although few in number, RCTs of respiratory muscle training found a significant reduction in bronchodilator medication use. Where meta-analyses could be done, they provided evidence of benefit from yoga, Buteyko breathing technique and physiotherapist-led breathing training in improving asthma-related quality of life. However, considerable heterogeneity was noted in some RCTs of yoga. It is reasonable for clinicians to offer qualified support to patients with asthma undertaking these breathing retraining techniques.

Panax ginseng C.A Meyer root extract for moderate chronic obstructive pulmonary disease (COPD): study protocol for a randomised controlled trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) impairs quality of life and leads to premature mortality. COPD sufferers experience progressive deterioration of lung function and decreased ability to undertake day-to-day activities. Ginseng has been used for thousands of years in Chinese medicine for respiratory symptoms. Several controlled clinical trials using ginseng for COPD have shown promising clinical effect, however these studies were generally small and with some potential bias, prompting the need for rigorously designed studies. AIM: The objective of this study is to evaluate the therapeutic value and safety profile of a standardised root extract of Panax ginseng C.A Meyer (ginseng) for symptomatic relief, with a focus on quality of life (QoL) improvements in individuals with moderate (Stage II) COPD FEV1/FVC < 0.7 and FEV1 50%-80% predicted. METHODS: This paper describes the design of a randomised, multi-centre, double-blind, placebo controlled, two-armed parallel clinical trial. Two trial sites in Melbourne Australia will proportionately randomise a total of 168 participants to receive either ginseng capsule (100 mg) or matching placebo twice daily for 24 weeks. The primary outcomes will be based on three validated QoL questionnaires, St Georges Respiratory Questionnaire (SGRQ), Short Form Health Survey (SF-36) and the COPD Assessment Test (CAT). Secondary outcomes are based on lung function testing, relief medication usage and exacerbation frequency and severity. Safety endpoints include blood tests and adverse event reporting. Intention-to-treat will be applied to all data analyses. DISCUSSION: Findings from this study may lead to new therapeutic development for chronic respiratory diseases, particularly COPD. This protocol may also guide other investigators to develop quality herbal medicine clinical trials in the future. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000768099.

Oral ginseng formulae for stable chronic obstructive pulmonary disease: a systematic review.

Ginseng alone or combined with other herbs has been increasingly used for chronic obstructive pulmonary disease (COPD). This review aims to evaluate the effectiveness and safety of oral Ginseng formulae for stable COPD. Four English databases and three Chinese databases were searched to identify randomized controlled trials. Methodological quality was assessed by Cochrane risk of bias and Jadad's scale. Data were analyzed using Review Manager 5.0. Twelve studies overall of low quality, involving 1560 participants were included. Results of three studies showed a mean difference (MD) of 0.30 (95%CI 0.02 to 0.58) for forced expiratory volume in 1 s (FEV(1)) improvement of Ginseng formulae versus placebo control. Findings of three studies revealed an MD of 9.43 (95%CI 3.64 to 15.21) of FEV(1) % predicted between Ginseng formulae and placebo control. Quality of life (Qol) measured by St. George's Respiratory Questionnaire was improved (MD -10.32, 95%CI -14.99 to -5.65) with Ginseng formulae plus pharmacotherapy versus pharmacotherapy alone in one study. There were no severe adverse events reported. Ginseng formulae for stable COPD patients show promising evidence of lung functions and Qol improvement. However, the degree of benefit is uncertain due to potential risk of bias of the included studies.

Inhibition of release of inflammatory mediators in rat peritoneal mast cells and murine macrophages by a Chinese herbal medicine formula (RCM-102).

RCM-102 is a Chinese herbal medicine formulation derived from a formula which was shown to be effective in treating seasonal allergic rhinitis (SAR) in a randomized placebo-controlled trial. The aim of this study was to investigate the in vitro effect of RCM-102 on the formation of inflammatory mediators, histamine, prostaglandin and nitric oxide, which are known to be involved in the pathophysiology of SAR. The effect of RCM-102 on histamine release was tested in compound 48/80-stimulated rat peritoneal mast cells. The effects of RCM-102 on the release of NO and prostaglandins (PGE(2)) and the expression of inducible NO synthase (iNOS) and COX-2 were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In rat peritoneal mast cells, RCM-102 significantly reduced the compound 48/80-induced histamine release. It also significantly reduced NO and PGE(2) production as well as the expression of COX-2 and iNOS in RAW 264.7 cells. These findings indicate that RCM-102 inhibits the formation of several allergic/inflammatory mediators and thus may be used for treating related conditions such as SAR. The actions of RCM-102 are likely to be contributed by the synergistic actions of individual herbal ingredients.

Inhibition of inducible nitric oxide production and iNOS protein expression in lipopolysaccharide-stimulated rat aorta and Raw 264.7 macrophages by ethanol extract of a Chinese herbal medicine formula (RCM-101) for allergic rhinitis.

AIM OF THE STUDY: A Chinese herbal formula (RCM-101) has shown to be effective in reducing symptoms of seasonal allergic rhinitis (SAR) in a randomised, placebo-controlled clinical trial. The aim of this study is to investigate the effects of RCM-101 on the actions and synthesis of nitric oxide (NO). l-Arginine-induced endothelium-independent relaxations were studied in rat isolated aorta which was pre-treated with lipopolysaccharide (LPS). MATERIALS AND METHODS: NO production and inducible nitric oxide synthase (iNOS) protein expression were studied in LPS and interferon gamma-stimulated murine macrophages (Raw 264.7), measured by NO sensors and Western blotting. RESULTS: In rat aortic preparations, RCM-101 significantly inhibited endothelium-independent relaxations to l-arginine, but not affected those to sodium nitroprusside (SNP). In Raw 264.7 cells, RCM-101 and some of its individual ingredients (e.g., Radix glycyrrhizae, Radix bupleuri, Radix saposhnikoviae and Atractylodis rhizome macrocephalae) significantly inhibited the NO production and iNOS protein expression. CONCLUSIONS: The findings indicate that RCM-101 may inhibit inducible NO production by suppressing iNOS. In addition, its inhibitory action of iNOS is likely to be mediated by several key herbal ingredients.

Inhibition of release of vasoactive and inflammatory mediators in airway and vascular tissues and macrophages by a chinese herbal medicine formula for allergic rhinitis.

Herbal therapies are being used increasingly for the treatment of allergic rhinitis. The aim of this study was to investigate the possible pharmacological actions and cellular targets of a Chinese herbal formula (RCM-101), which was previously shown to be effective in reducing seasonal allergic rhinitis symptoms in a randomized, placebo-controlled clinical trial. Rat and guinea pig isolated tissues (trachea and aorta) were used to study the effects of RCM-101 on responses to various mediators. Production of leukotriene B(4) in porcine neutrophils and of prostaglandin E(2) and nitric oxide (NO) in Raw 264.7 cells were also measured. In rat and guinea pig tracheal preparations, RCM-101 inhibited contractile responses to compound 48/80 but not those to histamine (guinea pig preparations) or serotonin (rat preparations). Contractile responses of guinea pig tracheal preparations to carbachol and leukotriene C(4,) and relaxant responses to substance P and prostaglandin E(2) were not affected by RCM-101. In rat aortic preparations, precontracted with phenylephrine, endothelium-dependent relaxant responses to acetylcholine and endothelium-independent relaxant responses to sodium nitroprusside were not affected by RCM-101. However, RCM-101 inhibited relaxations to l-arginine in endothelium-denuded rat aortic preparations, which had been pre-incubated with lipopolysaccharide. RCM-101 did not affect leukotriene B(4) formation in isolated porcine neutrophils, induced by the calcium ionophore A23187; however, it inhibited prostaglandin E(2) and NO production in lipopolysaccharide-stimulated murine macrophages (Raw 264.7 cells).The findings indicate that RCM-101 may have multiple inhibitory actions on the release and/or synthesis of inflammatory mediators involved in allergic rhinitis.

Treatment for seasonal allergic rhinitis by Chinese herbal medicine: a randomized placebo controlled trial.

CONTEXT: Chinese herbal medicine (CHM) is widely used to treat seasonal allergic rhinitis (SAR), however, evidence of efficacy is lacking. OBJECTIVE: To evaluate the efficacy of a Chinese herbal formulation for the treatment of SAR. DESIGN: Randomized, double blind, placebo controlled trial. SETTING: RMIT Chinese Medicine Clinic. PATIENTS: 55 patients with seasonal allergic rhinitis (active 28, placebo 27). INTERVENTIONS: CHM extract capsule (containing 18 herbs) or placebo, given daily for 8 weeks. MAIN OUTCOME MEASURES: The primary measure of efficacy were changes in severity of nasal and non-nasal symptoms using a Five Point Scale (FPS) measured by both patients and the practitioner. The secondary measure was the change in score for the domains measured in the Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire (RQLQ) assessed by patients. RESULTS: Forty-nine patients completed the study (active 24, placebo 25). After eight weeks, the severity of nasal symptoms and non-nasal symptoms were significantly less in the active treatment group than in the control group, both for measurements made by patients and those by the practitioner. Comparison of active and placebo treatment groups RQLQ scores also indicated significant beneficial effects of treatment (end point Section 1: P < 0.05; Section 2: P < 0.01). Intention-to-treat analyses of categorical items showed moderate to marked improvement rates were 60.7% and 29.6% for active and placebo respectively. Eleven patients reported mild adverse events including 1 withdrawn from the trial. CONCLUSIONS: This CHM formulation appears to offer symptomatic relief and improvement of quality of life for some patients with seasonal allergic rhinitis.