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,
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.
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.
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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
ABSTRACT
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 <3/year), asthma control using the Asthma Control Test (ACT) and quality of life using the Asthma Quality of Life Questionnaire (AQLQ). Multivariate logistic regression was performed for dichotomous outcomes and linear regression for continuous outcomes. Analyses were adjusted for lung function and absolute blood eosinophils.
Results
Increasing BMI was an independent risk factor for exacerbations (OR: 1.1, 95% CI: 1–1.1, P = 0.042), lower ACT score (β coefficient: −0.25, 95% CI: −0.37 to −0.12, P < 0.001) and poorer AQLQ (β coefficient: −0.05, 95% CI: −0.09 to −0.02, P = 0.006). DB predicted lower ACT (β coefficient: −2.85, 95% CI: −5 to −0.7, P = 0.01) and AQLQ scores (β coefficient: −0.73, 95% CI: −1.34 to −0.12, P = 0.02). Patients with CRS had more exacerbations (OR: 4, 95% CI: 1.5–10.9, P = 0.006). Patients with VCD had lower AQLQ scores (β coefficient: −0.78, 95% CI: −1.38 to −0.18, P = 0.012).
Conclusion
Comorbidities independently impact a broad spectrum of outcomes in difficult asthma. Systematic evaluation of these conditions is essential in difficult asthma.
This study examined comorbidities in a consecutive cohort of difficult asthma patients. Increasing BMI, chronic rhinosinusitis, dysfunctional breathing and vocal cord dysfunction were independent risk factors for a broad spectrum of asthma outcomes. Identification and treatment of these comorbidities are essential in management of patients with difficult asthma.
ABSTRACT
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.
We assessed the prevalence of treatable traits in severe asthma compared with non‐severe asthma, and assessed the relationship between treatable traits and future exacerbation risk. We demonstrate the usefulness of the treatable traits approach in severe asthma and which specific treatable traits are predictive of future asthma attacks.
See related Editorial
Background
Multidisciplinary systematic assessment improves outcomes in difficult‐to‐treat asthma, but without clear response predictors. Using a treatable‐traits framework, we stratified patients by ...trait profile, examining clinical impact and treatment responsiveness to systematic assessment.
Methods
We performed latent class analysis using 12 traits on difficult‐to‐treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ‐6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1, exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment.
Results
Among 241 patients, two airway‐centric profiles were characterized by early‐onset with allergic rhinitis (n = 46) and adult onset with eosinophilia/chronic rhinosinusitis (n = 60), respectively, with minimal comorbid or psychosocial traits; three non‐airway‐centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n = 51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n = 72), or multi‐domain impairment (n = 12). Compared to airway‐centric profiles, non‐airway‐centric profiles had worse baseline ACQ‐6 (2.7 vs. 2.2, p < .001) and AQLQ (3.8 vs. 4.5, p < .001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway‐centric profiles had more FEV1 improvement (5.6% vs. 2.2% predicted, p < .05) while non‐airway‐centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p = .07); mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p = .782).
Conclusion
Distinct trait profiles in difficult‐to‐treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult‐to‐treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.
We performed latent class analysis on 241 difficult‐to‐treat asthma patients undergoing systematic assessment at Alfred Health in Melbourne, Australia. Five trait profiles were identified, associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult‐to‐treat asthma, provide a conceptual framework to address disease heterogeneity, and identify areas responsive to targeted intervention.Abbreviations: ACQ‐6, Asthma Control Questionnaire; AQLQ, Asthma Quality of Life Questionnaire; FEV1, forced expiratory volume in one second; freq., frequency; OCS, oral corticosteroid
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.
To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR.
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.
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 FEV
. 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.
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.
Understanding of dysfunctional breathing in patients with difficult asthma who remain symptomatic despite maximal inhaler therapy is limited.
We characterized the pattern of dysfunctional breathing ...in patients with difficult asthma and identified possible contributory factors.
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.
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.
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.
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