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The controversy surrounding short-acting β2-agonist (SABA) monotherapy for very mild and mild asthma continues in guidelines despite increasing evidence in favor of combined inhaled corticosteroid/reliever therapy. We herein briefly review the findings from two high-quality randomized controlled trials and other safety data to conclude that the efficacy and safety of SABA monotherapy have been overstated, especially in type-2 high or allergic disease.

Cortical arousal-related hypopneas are not scored on type 3 home devices, which therefore limits their diagnostic accuracy for obstructive sleep apnea. The objective of this study was to evaluate whether scoring heart rate accelerations as surrogate markers of arousal improves type 3 portable monitor diagnostic agreement compared with polysomnography and improves therapeutic decision-making. We prospectively recruited patients evaluated for obstructive sleep apnea to undergo in-laboratory simultaneous full polysomnography + type 3 portable monitoring. Hypopnea events were scored on portable monitor studies with and without autonomic scoring, which was defined as an associated increase in pulse oximetry-derived heart rate ≥6 beats per min (autonomic hypopnea). Portable monitor diagnostic agreement compared with polysomnography with and without autonomic hypopnea scoring was assessed. We also evaluated whether reporting autonomic hypopnea scoring improves portable monitor clinical treatment decision agreement after four physicians reviewed clinical data and sleep study results (polysomnography, portable monitor with autonomic hypopnea, portable monitor without autonomic hypopnea). Eighty-two participants completed simultaneous polysomnography and in-laboratory portable monitor studies. Scoring autonomic hypopnea resulted in a decreased mean difference between in-laboratory portable monitor respiratory event index and polysomnography apnea-hypopnea index in Bland-Altman analysis (mean difference 14.6 per hr without versus 6.1 per hr with autonomic hypopnea scoring [p ˂ 0.01]), and increased intraclass correlation from 0.769 to 0.844. Inclusion of autonomic hypopnea scoring resulted in better accuracy between portable monitor and polysomnography expert's treatment decisions, and ultimately resulted in 24% fewer additional polysomnographies requested. The addition of pulse oximetry heart rate increases for autonomic hypopnea scoring during portable monitor resulted in better diagnostic agreement, improved clinical decision-making and reduced additional polysomnography testing.

Thunderstorm-triggered asthma (TA) is the occurrence of acute asthma attacks immediately following a thunderstorm. Epidemics have occurred across the world during pollen season and have the capacity to rapidly inundate a health care service, resulting in potentially catastrophic outcomes for patients. TA occurs when specific meteorological and aerobiological factors combine to affect predisposed patients. Thunderstorm outflows can concentrate aeroallergens, most commonly grass pollen in TA, at ground level to release respirable allergenic particles after rupture by osmotic shock related to humidity and rainfall. Inhalation of high concentrations of these aeroallergens by sensitized individuals can induce early asthmatic responses which are followed by a late inflammatory phase. Other environmental factors such as rapid temperature change and agricultural practices contribute to the causation of TA. The most lethal TA event occurred in Melbourne, Australia, in 2016. Studies on the affected individuals found TA to be associated with allergic rhinitis, ryegrass pollen sensitization, pre-existing asthma, poor adherence to inhaled corticosteroid preventer therapy, hospital admission for asthma in the previous year and outdoor location at the time of the storm. Patients without a prior history of asthma were also affected. These factors are important in extending our understanding of the etiology of TA and associated clinical indicators as well as possible biomarkers which may aid in predicting those at risk and thus those who should be targeted in prevention campaigns. Education on the importance of recognizing asthma symptoms, adherence to asthma treatment and controlling seasonal allergic rhinitis is vital in preventing TA. Consideration of allergen immunotherapy in selected patients may also mitigate risk of future TA. Epidemic TA events are predicted to increase in frequency and severity with climate change, and identifying susceptible patients and preventing poor outcomes is a key research and public health policy priority.

Simple Summary We recently developed an oncogenetic model to overcome the unprecedented demand for genetic counseling and testing for hereditary breast and ovarian cancer. Quality and performance indicators showed that the implementation of this model improved access to genetic counseling and minimized delays for genetic tests for patients, who reported to be overwhelmingly satisfied with the process. However, it remains unknown whether this model is robust and sustainable or requires adjustments. In addition, whether the model could be deployed elsewhere remains also to be elucidated. The C-MOnGene study was therefore designed to gain an in-depth understanding of the context in which the model was developed and implemented, and document the lessons that can be learned to optimize oncogenetic services delivery in other settings. Abstract Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants’ understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.

BACKGROUND In Canada, 30%-60% of patients presenting to emergency departments are ambulatory. This category has been labeled as a source of emergency department overuse. Acting on the presumption that primary care practices and walk-in clinics offer equivalent care at a lower cost, governments have invested massively in improving access to these alternative settings in the hope that patients would present there instead when possible, thereby reducing the load on emergency departments. Data in support of this approach remain scarce and equivocal. OBJECTIVE The aim of this study is to compare the value of care received in emergency departments, walk-in clinics, and primary care practices by ambulatory patients with upper respiratory tract infection, sinusitis, otitis media, tonsillitis, pharyngitis, bronchitis, influenza-like illness, pneumonia, acute asthma, or acute exacerbation of chronic obstructive pulmonary disease. METHODS A multicenter prospective cohort study will be performed in Ontario and Québec. In phase 1, a time-driven activity-based costing method will be applied at each of the 15 study sites. This method uses time as a cost driver to allocate direct costs (eg, medication), consumable expenditures (eg, needles), overhead costs (eg, building maintenance), and physician charges to patient care. Thus, the cost of a care episode will be proportional to the time spent receiving the care. At the end of this phase, a list of care process costs will be generated and used to calculate the cost of each consultation during phase 2, in which a prospective cohort of patients will be monitored to compare the care received in each setting. Patients aged 18 years and older, ambulatory throughout the care episode, and discharged to home with one of the aforementioned targeted diagnoses will be considered. The estimated sample size is 1485 patients. The 3 types of care settings will be compared on the basis of primary outcomes in terms of the proportion of return visits to any site 3 and 7 days after the initial visit and the mean cost of care. The secondary outcomes measured will include scores on patient-reported outcome and experience measures and mean costs borne wholly by patients. We will use multilevel generalized linear models to compare the care settings and an overlap weights approach to adjust for confounding factors related to age, sex, gender, ethnicity, comorbidities, registration with a family physician, socioeconomic status, and severity of illness. RESULTS Phase 1 will begin in 2021 and phase 2, in 2023. The results will be available in 2025. CONCLUSIONS The end point of our program will be for deciders, patients, and care providers to be able to determine the most appropriate care setting for the management of ambulatory emergency respiratory conditions, based on the quality and cost of care associated with each alternative. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/25619

Rationale: On November 21, 2016 in Australia, a major thunderstorm-asthma epidemic struck Melbourne with an unprecedented number of emergency presentations, hospital admissions and fatalities. Objectives: We identified affected patients who presented to The Royal Melbourne Hospital, an adult tertiary center in North-West Melbourne. We aimed to characterize individual patient factors associated with hospital admission and identify biomarkers in patient subgroups that are at risk of being severely affected by thunderstorm-asthma. Methods: Cross-sectional, retrospective analysis of demographics of 240 patients presenting to The Royal Melbourne Hospital on November 21 to 22, 2016 post thunderstorm-asthma event and clinical characteristics of 70 of those patients who subsequently attended an outpatient clinic review. Results: Patients were generally young adults (mean age 35 years), with seasonal rhinitis (96%) and universally (100%) sensitized to ryegrass pollen. Forty-four patients (63%) had a known diagnosis of asthma while 20% reported no previous diagnosis but had symptoms consistent with asthma. Patient characteristics associated with hospitalization were: uncontrolled asthma symptoms in the month before the thunderstorm-asthma event, symptomatic allergic rhinitis, high blood eosinophilia and lower lung function. Conclusion: Thunderstorm-asthma affects people with seasonal rhinitis, ryegrass sensitization and can occur without prior history of asthma, with dramatic potential to inundate a healthcare system. Our data suggests that hospitalization, and thus a more severe thunderstorm-asthma exacerbation, was associated with a known history of asthma, prior uncontrolled asthma symptoms, allergic rhinitis, high eosinophil count and lower lung function. These factors may inform strategies to identify those most at risk of thunderstorm-asthma.

Background The world's most catastrophic and deadly thunderstorm asthma epidemic struck Melbourne, Australia, on November 21, 2016. Objective Among thunderstorm-affected patients presenting to emergency rooms (ERs), we investigated risk factors predicting severe attacks requiring admission to hospital. Methods Thunderstorm-affected patients were identified from ER records at the eight major Melbourne health services and interviewed by telephone. Risk factors for hospital admission were analyzed. Results We interviewed 1435/2248 (64%) of thunderstorm-affected patients, of whom 164 (11.4%) required hospital admission. Overall, rhinitis was present in 87%, and current asthma was present in 28%. Odds for hospital admission were higher with increasing age (odds ratio 1.010, 95% CI 1.002, 1.019) and among individuals with current asthma (adjusted odds ratio [aOR] 1.87, 95% CI 1.26, 2.78). Prior hospitalization for asthma in the previous 12 months further increased the odds for hospital admission (aOR 3.16, 95% CI 1.63, 6.12). Among patients of Asian ethnicity, the odds for hospital admission were lower than for non-Asian patients (aOR 0.59, 95% CI 0.38, 0.94), but higher if born in Australia (OR = 5.42, 95% CI 1.56, 18.83). Conclusions In epidemic thunderstorm asthma patients who presented to the ER, higher odds for hospital admission among patients with known asthma were further amplified by recent asthma admission, highlighting the vulnerability conferred by suboptimal disease control. Odds for hospital admission were lower in Asian patients born overseas, but higher in Asian patients born locally, than in non-Asian patients; these observations suggest susceptibility to severe thunderstorm asthma may be enhanced by gene-environment interactions.

Type 3 home study (HS) monitors do not detect cortical arousal-related hypopneas and may therefore underestimate the polysomnography (PSG)-based apnea-hypopnea index (AHI). Our aim was to test the hypothesis that scoring hypopneas using heart rate accelerations as a surrogate marker for cortical arousal (autonomic hypopnea; AnH) improves the accuracy of HS for OSA diagnosis, using PSG AHI as the diagnostic gold standard. We retrospectively identified patients referred for OSA who underwent complete PSG following an initial inconclusive HS. Respiratory events were scored using AASM research (Chicago) criteria with additional HS scoring for AnH, defined as hypopneas based on flow criteria associated with an increase in pulse oximetry-derived heart rate ≥ 6 beats/min. A total of 178 patients met inclusion criteria, with mean (±SD) HS AHI = 4.4 ± 4.2/h, which increased to 8.5 ± 5.3/h with AnH scoring. The hypopnea arousal index on subsequent PSG was 7.6 ± 7.7/h, with total AHI 15.6 ± 11.9/h. Bland-Altman analysis showed improved agreement between HS and PSG AHI (mean difference 11.2/h (95%CI 33.6, − 11.1) without vs. 7.2/h (95%CI 29.6, − 15.4) with AnH scoring). Overall diagnostic accuracy was improved with AnH scoring as reflected by an increased area under the receiver-operating characteristic curve for AHI thresholds of 10 and 15 events/h. In this retrospective analysis, the diagnostic accuracy of type 3 HS was improved by the inclusion of hypopnea-associated heart rate increases as a surrogate marker of arousal. Prospective studies are warranted to evaluate the impact of AnH scoring on clinical decision-making and patient outcomes.

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/m 3 ). 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

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.

Thunderstorm-triggered asthma (TA) is the occurrence of acute asthma attacks immediately following a thunderstorm. Epidemics have occurred across the world during pollen season and have the capacity to rapidly inundate a health care service, resulting in potentially catastrophic outcomes for patients. TA occurs when specific meteorological and aerobiological factors combine to affect predisposed patients. Thunderstorm outflows can concentrate aeroallergens, most commonly grass pollen in TA, at ground level to release respirable allergenic particles after rupture by osmotic shock related to humidity and rainfall. Inhalation of high concentrations of these aeroallergens by sensitized individuals can induce early asthmatic responses which are followed by a late inflammatory phase. Other environmental factors such as rapid temperature change and agricultural practices contribute to the causation of TA. The most lethal TA event occurred in Melbourne, Australia, in 2016. Studies on the affected individuals found TA to be associated with allergic rhinitis, ryegrass pollen sensitization, pre-existing asthma, poor adherence to inhaled corticosteroid preventer therapy, hospital admission for asthma in the previous year and outdoor location at the time of the storm. Patients without a prior history of asthma were also affected. These factors are important in extending our understanding of the etiology of TA and associated clinical indicators as well as possible biomarkers which may aid in predicting those at risk and thus those who should be targeted in prevention campaigns. Education on the importance of recognizing asthma symptoms, adherence to asthma treatment and controlling seasonal allergic rhinitis is vital in preventing TA. Consideration of allergen immunotherapy in selected patients may also mitigate risk of future TA. Epidemic TA events are predicted to increase in frequency and severity with climate change, and identifying susceptible patients and preventing poor outcomes is a key research and public health policy priority.

This study sought to evaluate whether the partial implementation of an Early Recovery After Surgery (ERAS) program lowers length of hospital stay (LOS) without compromising postoperative outcome.A single-centre prospective cohort study was conducted in a tertiary gynaecologic oncology department, by comparing standard perioperative care with a partially implemented ERAS protocol. Data on postoperative evolution were gathered for patients who underwent laparotomy for suspected or confirmed endometrial, adnexal, or cervical neoplasia between July 1, 2015 and June 30, 2017 at the Hôtel-Dieu de Québec.A total of 390 cases were identified; 140 patients followed the ERAS protocol, and 250 patients received standard perioperative care. The median LOS in hours was significantly reduced for patients in the ERAS group (65.5 hours [interquartile range 59.8, 71.0] vs. 69.0 hours [interquartile range 64.3, 81.0], P 0.001). There was no difference in complication rates, neither grade 1 (3% vs. 7%, P = 0.155) nor grades 2 to 4 (7% vs. 5%, P = 0.577), or in readmission rates (0.7% vs. 1.2%, P0.99).Even a partially implemented ERAS program can significantly affect LOS without compromising patient care.

The transforming growth factor (TGF)-β cytokines play a central role in development and progression of chronic respiratory diseases. TGF-β overexpression in chronic inflammation, remodeling, fibrotic process and susceptibility to viral infection is established in the most prevalent chronic respiratory diseases including asthma, COPD, lung cancer and idiopathic pulmonary fibrosis. Despite the overwhelming burden of respiratory diseases in the world, new pharmacological therapies have been limited in impact. Although TGF-β inhibition as a therapeutic strategy carries great expectations, the constraints in avoiding compromising the beneficial pleiotropic effects of TGF-β, including the anti-proliferative and immune suppressive effects, have limited the development of effective pharmacological modulators. In this review, we focus on the pathways subserving deleterious and beneficial TGF-β effects to identify strategies for selective modulation of more distal signaling pathways that may result in agents with improved safety/efficacy profiles. Adverse effects of TGF-β inhibitors in respiratory clinical trials are comprehensively reviewed, including those of the marketed TGF-β modulators, pirfenidone and nintedanib. Precise modulation of TGF-β signaling may result in new safer therapies for chronic respiratory diseases.

Coal workers' pneumoconiosis (CWP), as part of the spectrum of coal mine dust lung disease (CMDLD), is a preventable but incurable lung disease that can be complicated by respiratory failure and death. Recent increases in coal production from the financial incentive of economic growth lead to higher respirable coal and quartz dust levels, often associated with mechanization of longwall coal mining. In Australia, the observed increase in the number of new CWP diagnoses since the year 2000 has necessitated a review of recommended respirable dust exposure limits, where exposure limits and monitoring protocols should ideally be standardized. Evidence that considers the regulation of engineering dust controls in the mines is lacking even in high-income countries, despite this being the primary preventative measure. Also, it is a global public health priority for at-risk miners to be systemically screened to detect early changes of CWP and to include confirmed patients within a central registry; a task limited by financial constraints in less developed countries. Characteristic X-ray changes are usually categorized using the International Labour Office classification, although future evaluation by low-dose HRCT) chest scanning may allow for CWP detection and thus avoidance of further exposure, at an earlier stage. Preclinical animal and human organoid-based models are required to explore potential re-purposing of anti-fibrotic and related agents with potential efficacy. Epidemiological patterns and the assessment of molecular and genetic biomarkers may further enhance our capacity to identify susceptible individuals to the inhalation of coal dust in the modern era.

† Background and Aims Previous work has shown that the entire photosynthetic light response curve, based on both Mitscherlich and Michaelis –Menten functions, could be predicted in an interspecific context through allometric relations linking the parameters of these functions to two static leaf traits: leaf nitrogen (N) content and leaf mass per area (LMA). This paper describes to what extent these allometric relations are robust to changes in soil fertility and the growth irradiance of the plants. † Methods Plants of 25 herbaceous species were grown under controlled conditions in factorial combinations of low/high soil fertility and low/high growth irradiance. Net photosynthetic rates per unit dry mass were measured at light intensities ranging from 0 to 700 mmol m 22 s 21 photosynthetically active radiation (PAR). † Key Results The differing growth environments induced large changes in N, LMA and in each of the parameter estimates of the Mitscherlich and Michaelis–Menten functions. However, the differing growth environments induced only small (although significant) changes in the allometric relationships linking N and LMA to the parameters of the two functions. As a result, 88 % (Mitcherlich) and 89 % (Michaelis –Menten) of the observed net photosynthetic rates over the full range of light intensities (0–700 mmol m 22 s 21 PAR) and across all four growth environments could be predicted using only N and LMA using the same allometric relations. † Conclusions These results suggest the possibility of predicting net photosynthetic rates in nature across species over the full range of light intensities using readily available data.