Chest x-ray has low sensitivity to detect silicosis in artificial stone benchtop industry workers.

BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.

Psychometric properties of the Perceived Stress Scale (PSS-10) in silica-exposed workers from diverse cultural and linguistic backgrounds.

BACKGROUND: The Perceived Stress Scale (PSS-10) has been used in a range of occupational cohorts, but only recently in stone benchtop workers undergoing screening for silicosis. The aim of this study was to compare psychometric properties of the PSS-10 in stone benchtop workers amongst those born overseas or who used an interpreter. METHODS: Stone benchtop workers in Melbourne, Australia completed the PSS-10 as part of their occupational screening for silicosis. Internal consistency was assessed with Cronbach's α for the total score and the positive and negative subscales. Validity was assessed using confirmatory factor analysis (CFA). Analysis was performed for the total group and for subgroups according to sex, interpreter use, overseas-born, and language spoken at home. RESULTS: The results of 682 workers with complete PSS-10 scores were included in analysis. Most participants were male (93%), with mean age 36.9 years (SD 11.4), with just over half (51.6%) born in Australia, 10.1% using an interpreter, and 17.5% using a language other than English at home. Cronbach's α for the overall group (α = 0.878) suggested good internal consistency. DISCUSSION: CFA analysis for validity testing suggested PSS-10 performance was good for both sexes, moderate for country of birth and language spoken at home categories, but poorer for those who used an interpreter. Whilst professional interpreters provide a range of benefits in the clinical setting, the use of translated and validated instruments are important, particularly in cohorts with large numbers of migrant workers. CONCLUSION: This study describes the psychometric properties of the PSS-10 in a population of stone benchtop workers, with good internal consistency, and mixed performance from validity testing across various subgroups.

Prevalence and risk factors for silicosis among a large cohort of stone benchtop industry workers.

OBJECTIVES: High silica content artificial stone has been found to be associated with silicosis among stone benchtop industry (SBI) workers. The objectives of this study were to determine the prevalence of and risk factors for silicosis among a large cohort of screened SBI workers, and determine the reliability of respiratory function testing (RFT) and chest x-ray (CXR) as screening tests in this industry. METHODS: Subjects were recruited from a health screening programme available to all SBI workers in Victoria, Australia. Workers undertook primary screening, including an International Labour Office (ILO) classified CXR, and subject to prespecified criteria, also underwent secondary screening including high-resolution CT (HRCT) chest and respiratory physician assessment. RESULTS: Among 544 SBI workers screened, 95% worked with artificial stone and 86.2% were exposed to dry processing of stone. Seventy-six per cent (414) required secondary screening, among whom 117 (28.2%) were diagnosed with silicosis (median age at diagnosis 42.1 years (IQR 34.8-49.7)), and all were male. In secondary screening, silicosis was associated with longer SBI career duration (12 vs 8 years), older age, lower body mass index and smoking. In those with silicosis, forced vital capacity was below the lower limit of normal in only 14% and diffusion capacity for carbon monoxide in 13%. Thirty-six (39.6%) of those with simple silicosis on chest HRCT had an ILO category 0 CXR. CONCLUSION: Screening this large cohort of SBI workers identified exposure to dry processing of stone was common and the prevalence of silicosis was high. Compared with HRCT chest, CXR and RFTs had limited value in screening this high-risk population.

Trait profiles in difficult-to-treat asthma: Clinical impact and response to systematic assessment.

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.

Predictors of psychological stress in silica-exposed workers in the artificial stone benchtop industry.

BACKGROUND AND OBJECTIVE: Artificial stone benchtops are a popular kitchen product, but dust from their preparation and installation contains respirable crystalline silica, which causes silicosis. Silicosis is a preventable, permanent lung disease. The aim of this study was to assess mental health in workers from the artificial stone benchtop industry at risk of silicosis. METHODS: Workers from the artificial stone benchtop industry undergoing assessment for silica-associated disease were included. Information on demographics; occupational, medical and smoking history; modified Medical Research Council dyspnoea scale; Perceived Stress Scale (PSS-10) questionnaire; spirometry; and chest x-ray was collected. Univariate and multivariate regression analyses were conducted. RESULTS: Of the 547 participants, the majority were men, aged under 45 years, in the industry for less than 10 years. With each increase of dyspnoea score, PSS-10 scores increased. Higher PSS-10 scores were also observed in those no longer in the industry, with a history of anxiety or depression, attending assessment early in the programme and a medium exposure duration. Participants who used an interpreter reported lower stress. No difference was observed across job title, age, sex, smoking, spirometry or chest x-ray categories after multivariate analysis. CONCLUSION: This study identified workers with dyspnoea as likely to report higher stress. Other factors, such as leaving the industry, early attendance and a history of anxiety or depression, are also helpful in identifying workers at risk of poorer mental health outcomes.

Silica Exposure Estimates in Artificial Stone Benchtop Fabrication and Adverse Respiratory Outcomes.

Silicosis is being increasingly reported among young stonemasons in the artificial stone (AS) benchtop fabrication and installation industry. Respiratory health screening, which included a job and exposure history, a chest X-ray (CXR), a respiratory health questionnaire, and gas transfer testing, were offered to stonemasons in Victoria, Australia. Workers typically reported a variety of tasks, including cleaning and labouring, which made exposure assessment complex. We estimated the relative respirable crystalline silica exposure intensity of each job from the proportion of time using AS and the proportion of time doing dry work (work without water suppression). The relative average intensity of exposure for up to five jobs was calculated. Cumulative exposure was calculated as the sum of the duration multiplied by intensity for each job. Installers and factory machinists (other than computer numeric control operators) were the most likely to report dry work with AS, and so had a greater average intensity of exposure. Exposure intensity and cumulative exposure were associated with increased odds of an ILO (International Labour Organisation) CXR profusion major category of ≥1 and with dyspnoea. Exposure duration was also associated with ILO profusion category. In multivariate analyses of health outcomes, only job type was associated with the ILO profusion category. For both most recent and longest-duration job types, when compared to the lowest exposure group, factory machinists were more likely to have an ILO category ≥1. This suggests that intensity of exposure estimated from the proportion of time dry cutting and proportion of time working on AS can predict the risk of adverse respiratory outcomes for workers in this industry.

Cluster Analysis of Inflammatory Biomarker Expression in the International Severe Asthma Registry.

BACKGROUND: Allergy, eosinophilic inflammation, and epithelial dysregulation are implicated in severe asthma pathogenesis. OBJECTIVE: We characterized biomarker expression in adults with severe asthma. METHODS: Within the International Severe Asthma Registry (ISAR), we analyzed data from 10 countries in North America, Europe, and Asia, with prespecified thresholds for biomarker positivity (serum IgE ≥ 75 kU/L, blood eosinophils ≥ 300 cells/µL, and FeNO ≥ 25 ppb), and with hierarchical cluster analysis using biomarkers as continuous variables. RESULTS: Of 1,175 patients; 64% were female, age (mean ± SD) 53 ± 15 years, body mass index (BMI) 30 ± 8, postbronchodilator forced expiratory volume in 1 second (FEV1) predicted 72% ± 20%. By prespecified thresholds, 59% were IgE positive, 57% eosinophil positive, and 58% FeNO positive. There was substantial inflammatory biomarker overlap; 59% were positive for either 2 or 3 biomarkers. Five distinct clusters were identified: cluster 1 (61%, low-to-medium biomarkers) comprised highly symptomatic, older females with elevated BMI and frequent exacerbations; cluster 2 (18%, elevated eosinophils and FeNO) older females with lower BMI and frequent exacerbations; cluster 3 (14%, extremely high FeNO) older, highly symptomatic, lower BMI, and preserved lung function; cluster 4 (6%, extremely high IgE) younger, long duration of asthma, elevated BMI, and poor lung function; cluster 5 (1.2%, extremely high eosinophils) younger males with low BMI, poor lung function, and high burden of sinonasal disease and polyposis. CONCLUSIONS: There is significant overlap of biomarker positivity in severe asthma. Distinct clusters according to biomarker expression exhibit unique clinical characteristics, suggesting the occurrence of discrete patterns of underlying inflammatory pathway activation and providing pathogenic insights relevant to the era of monoclonal biologics.

Identification of early-stage silicosis through health screening of stone benchtop industry workers in Victoria, Australia.

OBJECTIVES: The popularity of high silica content artificial stone has been associated with emergence of severe, progressive silicosis as a major health issue affecting workers in the stone benchtop industry. This population-based health assessment programme has been implemented with the aim of identifcation of silica-associated disease at a preclinical stage. METHODS: All current and former workers from the stone benchtop industry in the State of Victoria are offered free health assessments. Primary evaluations include a standardised questionnaire, physical examination, spirometry and gas transfer assessment and International Labour Organisation-categorised chest X-ray. Secondary evaluations include high-resolution CT chest, blood tests and a respiratory physician evaluation. RESULTS: At the end of the first 12 months, 86/239 (36%) workers who had completed secondary evaluation were diagnosed with silicosis (65 simple silicosis and 21 complicated silicosis). 22 had worked in the industry for less than 10 years at the time of diagnosis. Of those with simple silicosis, 80% of workers reported breathlessness only with strenuous exercise (modified Medical Research Council score of 0), and lung function was well preserved (prebronchodilator forced vital capacity mean 99.8% predicted (SD 13.6), diffusion capacity of the lung for carbon monoxide mean 96.2% predicted (SD 18.0)). Antinuclear antibodies were detected in 37% with silicosis and 24% without silicosis. CONCLUSION: Early results from this comprehensive health assessment programme have indicated a high proportion of referred artificial stone benchtop workers have silicosis, including many with early-stage disease. The common finding of antinuclear antibodies suggest significant potential for autoimmune disease in this occupational group.

Paradoxical Vocal Fold Motion in Difficult Asthma Is Associated with Dysfunctional Breathing and Preserved Lung Function.

BACKGROUND: Many patients with difficult asthma also have coexisting vocal cord dysfunction (VCD), evident by paradoxical vocal fold motion (PVFM) on laryngoscopy. OBJECTIVE: Among patients with difficult asthma, we sought to identify clinical features associated with laryngoscopy-diagnosed PVFM. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Systematic Assessment for Difficult and Severe Asthma Improves Outcomes and Halves Oral Corticosteroid Burden Independent of Monoclonal Biologic Use.

BACKGROUND: Guidelines endorse systematic assessment for severe asthma, with data indicating benefit across multiple outcome domains. OBJECTIVE: We examined which patients respond to systematic assessment and whether oral corticosteroid burden can be decreased independent of monoclonal biologic use. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Predominantly Antibody-Deficient Patients With Non-infectious Complications Have Reduced Naive B, Treg, Th17, and Tfh17 Cells.

Background: Patients with predominantly antibody deficiency (PAD) suffer from severe and recurrent infections that require lifelong immunoglobulin replacement and prophylactic antibiotic treatment. Disease incidence is estimated to be 1:25,000 worldwide, and up to 68% of patients develop non-infectious complications (NIC) including autoimmunity, which are difficult to treat, causing high morbidity, and early mortality. Currently, the etiology of NIC is unknown, and there are no diagnostic and prognostic markers to identify patients at risk. Objectives: To identify immune cell markers that associate with NIC in PAD patients. Methods: We developed a standardized 11-color flow cytometry panel that was utilized for in-depth analysis of B and T cells in 62 adult PAD patients and 59 age-matched controls. Results: Nine males had mutations in Bruton's tyrosine kinase (BTK) and were defined as having X-linked agammaglobulinemia. The remaining 53 patients were not genetically defined and were clinically diagnosed with agammaglobulinemia (n = 1), common variable immunodeficiency (CVID) (n = 32), hypogammaglobulinemia (n = 13), IgG subclass deficiency (n = 1), and specific polysaccharide antibody deficiency (n = 6). Of the 53, 30 (57%) had one or more NICs, 24 patients had reduced B-cell numbers, and 17 had reduced T-cell numbers. Both PAD-NIC and PAD+NIC groups had significantly reduced Ig class-switched memory B cells and naive CD4 and CD8 T-cell numbers. Naive and IgM memory B cells, Treg, Th17, and Tfh17 cells were specifically reduced in the PAD+NIC group. CD21lo B cells and Tfh cells were increased in frequencies, but not in absolute numbers in PAD+NIC. Conclusion: The previously reported increased frequencies of CD21lo B cells and Tfh cells are the indirect result of reduced naive B-cell and T-cell numbers. Hence, correct interpretation of immunophenotyping of immunodeficiencies is critically dependent on absolute cell counts. Finally, the defects in naive B- and T-cell numbers suggest a mild combined immunodeficiency in PAD patients with NIC. Together with the reductions in Th17, Treg, and Tfh17 numbers, these key differences could be utilized as biomarkers to support definitive diagnosis and to predict for disease progression.

Impaired STAT3-Dependent Upregulation of IL2Rα in B Cells of a Patient With a STAT1 Gain-of-Function Mutation.

Heterozygous STAT1 gain-of-function (GOF) mutations form the most common genetic cause of chronic mucocutaneous candidiasis (CMC). In such patients, increased STAT1 function leads to impaired STAT3-dependent activation of IL-17A and IL-17F in T cells, thereby causing impaired Th17 responses to Candida. In spite of the critical role of STAT3 in IL-21 signaling in B cells, nearly all STAT1 GOF patients have normal or high serum IgG. We here present a 44 year-old male with childhood onset of CMC and antibody deficiency since early adulthood. Sequence analysis of STAT1 revealed a heterozygous missense mutation in the coiled-coil domain (p.D168E), which resulted in increased STAT1 phosphorylation of B-cells activated with IFNα and IFNγ. IL-21 induced STAT3 phosphorylation and nuclear localization were normal, but resulted in impaired upregulation of IL2Rα. This newly identified B-cell intrinsic impairment of STAT3 function could underlie the progressive development of hypogammaglobulinemia. Considering the high risk of bronchiectasis and irreversible organ damage, this case illustrates the need for monitoring of IgG levels and/or function in adult patients with STAT1 GOF mutations.

Severe Asthma Global Evaluation (SAGE): An Electronic Platform for Severe Asthma.

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.

Factors Associated with Dysfunctional Breathing in Patients with Difficult to Treat Asthma.

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.

Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults.

Background: Predominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy. Objectives: To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. Methods: We identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features. Results: 179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16-87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort. Conclusion: Our data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.

Nonadherence in the era of severe asthma biologics and thermoplasty.

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.

A Structured Approach to Specialist-referred Difficult Asthma Patients Improves Control of Comorbidities and Enhances Asthma Outcomes.

BACKGROUND: Systematic evaluation is advocated for difficult asthma, but how best to deliver such care is unclear and outcome data are scarce. OBJECTIVE: We describe our institution's structured approach to difficult asthma management and report on the outcomes of such an approach. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Validated questionnaires heighten detection of difficult asthma comorbidities.

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.

Comorbidities in difficult asthma are independent risk factors for frequent exacerbations, poor control and diminished quality of life.

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 (ß coefficient: -0.25, 95% CI: -0.37 to -0.12, P < 0.001) and poorer AQLQ (ß coefficient: -0.05, 95% CI: -0.09 to -0.02, P = 0.006). DB predicted lower ACT (ß coefficient: -2.85, 95% CI: -5 to -0.7, P = 0.01) and AQLQ scores (ß 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 (ß 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.