For many respiratory physicians, point-of-care chest ultrasound is now an integral part of clinical practice. The diagnostic accuracy of ultrasound to detect abnormalities of the pleura, the lung ...parenchyma and the thoracic musculoskeletal system is well described. However, the efficacy of a test extends beyond just diagnostic accuracy. The true value of a test depends on the degree to which diagnostic accuracy efficacy influences decision-making efficacy, and the subsequent extent to which this impacts health outcome efficacy. We therefore reviewed the demonstrable levels of test efficacy for bedside ultrasound of the pleura, lung parenchyma and thoracic musculoskeletal system.For bedside ultrasound of the pleura, there is evidence supporting diagnostic accuracy efficacy, decision-making efficacy and health outcome efficacy, predominantly in guiding pleural interventions. For the lung parenchyma, chest ultrasound has an impact on diagnostic accuracy and decision-making for patients presenting with acute respiratory failure or breathlessness, but there are no data as yet on actual health outcomes. For ultrasound of the thoracic musculoskeletal system, there is robust evidence only for diagnostic accuracy efficacy.We therefore outline avenues to further validate bedside chest ultrasound beyond diagnostic accuracy, with an emphasis on confirming enhanced health outcomes.
ABSTRACT
OCS play an important role in the management of asthma. However, steroid‐related AE are common and represent a leading cause of morbidity. Limited published studies suggest OCS usage varies ...across countries and recent registry data indicate that at least 25–60% of patients with severe asthma in developed countries may at some stage be prescribed OCS. Recent evidence indicate that many patients do not receive optimal therapy for asthma and are often prescribed maintenance OCS or repeated steroid bursts to treat exacerbations. Given the recent progress in adult severe asthma and new treatment options, judicious appraisal of steroid use is merited. A number of strategies and add‐on therapies are now available to treat severe asthma. These include increasing specialist referral for multidisciplinary assessments and implementing OCS‐sparing interventions, such as improving guideline adherence and add‐on tiotropium and macrolides. Biologics have recently become available for severe asthma; these agents reduce asthma exacerbations and lower OCS exposure. Further research, collaboration and consensus are necessary to develop a structured stewardship approach including realistic OCS‐weaning programmes for patients with severe asthma on regular OCS; education and public health campaigns to improve timely access to specialized severe asthma services for treatment optimization; and implementing targeted strategies to identify patients who warrant OCS use using objective biomarker‐based strategies.
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
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); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33-0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.
The Melbourne thunderstorm asthma epidemic in November 2016 was unprecedented in scale and impact. We systematically reviewed our hospital's patients with thunderstorm asthma to identify key risk ...factors. Of 85 adult patients assessed, the majority (60%) had no prior diagnosis of asthma. However, allergic rhinitis during the grass pollen season was almost universal (99%), as were ryegrass pollen sensitization (100%) and exposure to the outdoor environment during the thunderstorm (94%). Airborne pollen levels on the thunderstorm day were extreme. We conclude that ryegrass pollen sensitization, clinical allergic rhinitis, and acute allergen exposure constitute a risk-factor ‘trifecta’ for thunderstorm asthma.
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•Ryegrass pollen sensitizsation, allergic rhinitis and allergen exposure are a risk ‘trifecta’ for thunderstorm asthma.•In contrast, the majority (60%) of patients presenting with thunderstorm asthma did not have a prior diagnosis of asthma.•The development of public health measures to target these identified key risk factors are essential to mitigate future risk.
Background Severe asthma causes the majority of asthma morbidity. Understanding mechanisms that contribute to the development of severe disease is important. Objective The goal of the Severe Asthma ...Research Program is to identify and characterize subjects with severe asthma to understand pathophysiologic mechanisms in severe asthma. Methods We performed a comprehensive phenotypic characterization (questionnaires, atopy and pulmonary function testing, phlebotomy, exhaled nitric oxide) in subjects with severe and not severe asthma. Results A total of 438 subjects with asthma were studied (204 severe, 70 moderate, 164 mild). Severe subjects with asthma were older with longer disease duration ( P < .0001), more daily symptoms, intense urgent health care utilization, sinusitis, and pneumonia ( P ≤ .0001). Lung function was lower in severe asthma with marked bronchodilator reversibility ( P < .001). The severe group had less atopy by skin tests ( P = .0007), but blood eosinophils, IgE, and exhaled nitric oxide levels did not differentiate disease severity. A reduced FEV1 , history of pneumonia, and fewer positive skin tests were risk factors for severe disease. Early disease onset (age < 12 years) in severe asthma was associated with longer disease duration ( P < .0001) and more urgent health care, especially intensive care ( P = .002). Later disease onset (age ≥ 12 years) was associated with lower lung function and sinopulmonary infections ( P ≤ .02). Conclusion Severe asthma is characterized by abnormal lung function that is responsive to bronchodilators, a history of sinopulmonary infections, persistent symptoms, and increased health care utilization. Clinical implications Lung function abnormalities in severe asthma are reversible in most patients, and pneumonia is a risk factor for the development of severe disease.
Background
While treatment for atopic rhinitis is aimed mostly to relieve symptoms, only allergen‐specific immunotherapy (AIT) is targeted to modify the natural history of allergic diseases. This ...results in sustained clinical tolerance, even when treatment has stopped. The immunomodulatory effects of AIT are attributed mainly to increased regulatory T‐cell function and increased allergen‐specific IgG4, yet little is known about the effect on the memory B‐cell compartment.
Objective
We aimed to examine the effects of AIT on the IgE‐ and IgG subclass‐expressing memory B cells.
Methods
We recruited 29 patients with atopic seasonal rhinoconjunctivitis and performed a longitudinal analysis of the peripheral immune compartment before, during, and after sublingual immunotherapy (SLIT) for allergy to temperate grass pollen, predominantly to ryegrass pollen (RGP; Lolium perenne). Using flow cytometry on peripheral blood mononuclear cells and serum immunoassays, we analyzed the effects of a 4 months preseasonal treatment regimen comprising two or three courses in consecutive years on circulating IgE+ and IgG+ memory B cells and allergen‐specific Ig levels.
Results
SLIT increased RGP‐specific serum IgG2 and IgG4, as well as the frequencies of IgG2+ and IgG4+ memory B cells, whereas no effect was observed on the IgE+ memory B‐cell compartment. Furthermore, SLIT enhanced proportions of regulatory T cells specific to RGP. These changes were associated with clinical improvement.
Conclusion
Our data provide evidence for immunological effects of SLIT on B‐cell memory. Skewing responses toward IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses.
This study examines the effect of ryegrass pollen AIT on B‐cell responses in a population of 29 patients with allergic rhinitis. Successful immunotherapy for ryegrass pollen allergy increases allergen‐specific IgG2 and IgG4 serum levels, and proportions of IgG2‐ and IgG4‐expressing memory B cells. Skewing toward the anti‐inflammatory IgG2 and IgG4 subclasses might be a mechanism to suppress IgE‐mediated allergic responses.
In chronic obstructive pulmonary disease (COPD), loss of computed tomography (CT)-measured intercostal mass correlates with spirometric severity. Intercostal muscle ultrasound offers a repeatable and ...radiation-free alternative, however requires validation. We aimed to determine the reliability of parasternal intercostal muscle ultrasound, and the concurrent validity of parasternal ultrasound with clinicometric parameters. Twenty stable COPD patients underwent ultrasound measurement of thickness and echogenicity of 2
and 3
parasternal intercostal muscles, dominant pectoralis major and quadriceps, and diaphragm thickness; spirometry; and chest CT. Intra-rater intraclass correlation (ICC) for ultrasound intercostal thickness was 0.87-0.97 depending on site, with echogenicity ICC 0.63-0.91. Inter-rater ICC was fair to excellent. Ultrasound intercostal thickness moderately correlated with FEV
% predicted (r = 0.33) and quadriceps thickness (r = 0.31). Echogenicity correlated negatively with FEV
% predicted (r = -0.32). CT-measured lateral intercostal mass correlate negatively with parasternal ultrasound intercostal thickness. These data confirm ultrasound of parasternal intercostal musculature is reproducible. Lower intercostal muscle quantity and quality reflects greater COPD spirometric severity. This novel tool may have biomarker potential for both the systemic effects of COPD on muscle as well as local disruption of respiratory mechanics. The negative correlation between CT and ultrasound measurements may reflect complex site-dependent interactions between respiratory muscles and the chest wall.
Background An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene B.sub.4 (LTB.sub.4), and lipoxin ...A.sub.4 (LXA.sub.4) production by alveolar macrophages (AMs) and studied the impact of corticosteroids. Methods AMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 mug/ml) with or without dexamethasone (10.sup.-6M). LTB.sub.4 and LXA.sub.4 were measured by enzyme immunoassay. Results LXA.sub.4 biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA.sub.4 induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTB.sub.4 were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTB.sub.4 was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTB.sub.4 and LXA.sub.4, with lesser suppression of LTB.sub.4 in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA.sub.4 and FEV.sub.1 (% predicted) (r.sub.s = 0.60; p < 0.01). Conclusions Decreased LXA.sub.4 and increased LTB.sub.4 generation plus impaired corticosteroid sensitivity of LPS-induced LTB.sub.4 but not of LXA.sub.4 support a role for AMs in establishing a pro-inflammatory balance in severe asthma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Currently there is no consistent and widely accepted approach to the diagnosis of vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO). Harmonised diagnostic methods are vital to enable ...optimal diagnosis, advance management and enable research. We aim to obtain consensus on how expert clinicians recognise and diagnose VCD/ILO.
Two-round modified Delphi, with workshop validation.
Institutional Board Review was obtained from the Monash Health Human Research Ethics Committee. The dissemination plan is for presentation and publication.
Registered at Australia and New Zealand Clinical Trials Registry ACTRN12621001520820p.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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