Home spirometry appears accurate and feasible for monitoring chronic respiratory disease.

Spirometry is underutilised and can be difficult to access. This study assessed the accuracy and feasibility of home spirometry compared to gold standard. Findings suggest home spirometry is accurate and feasible across many respiratory disease groups. https://bit.ly/42TLoYd.

Untangling asthma, inducible laryngeal obstruction, and dysfunctional breathing in a competitive sportsperson.

A young woman with historically mild asthma experienced worsening breathlessness and cough with competitive ice skating. Despite optimizing and escalating treatment for her eosinophilic asthma, and addressing known exacerbating factors, her symptoms remained uncontrolled and refractory to bronchodilators and oral corticosteroids. Objective testing suggested her presentation was out of keeping with asthma alone, and she was suspected to have comorbid dysfunctional breathing and/or inducible laryngeal obstruction. Evidence was required to confirm the diagnoses, assess each condition's contribution to her symptom burden, and guide therapy. As exercise was a predominant trigger, she proceeded to cardiopulmonary exercise test with continuous laryngoscopy during exercise (CPET-CLE). Testing confirmed the presence of two forms of inducible laryngeal obstruction and evidence of hyperventilation predominant dysfunctional breathing. This case highlights the importance of identifying coexisting conditions in difficult-to-treat asthma, and the value of structured multidisciplinary assessment in referral centres for such individuals.

Asthma control conundrum in clinical practice - Data from a two-stage Delphi survey and literature review.

Definitions and measures of asthma control used in clinical trials and practice often vary, as highlighted in the manuscript, "Is asthma control more than just an absence of symptoms? An expert consensus statement". Furthermore, the authors discussed differences between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma. Given these disparities, there is a need for consensus regarding what constitutes well-controlled asthma and, especially, how best it can be measured and recorded. In the current work, we describe our data and provide more detail on the methodology from a two-stage Delphi survey and a structured literature review, which were designed to reach a consensus definition of asthma control and alleviate misalignments between patients and HCPs. Survey data were collected using a two-stage Delphi technique; a method used to collate expert opinions over a series of sequential questionnaires to reach a consensus. The collated Delphi survey data were compared with results from a comprehensive, structured literature review of 216 publications, to assess if there was a correlation between existing guidance and measures of asthma control used in clinical trials and standard clinical practice. In order to collate and interpret findings from the Delphi survey, responses from 82 panelists (73 HCPs and 9 authors) were qualitatively analyzed, quantitatively categorized, and presented as percentages or counts in Excel databases, which are detailed in the current work. Searches conducted using PubMed and Cochrane identified 664 manuscripts, and Embase was used to identify 89 congress abstracts. After applying a stringent screening method using predefined key words, the structured literature review consisted of 185 peer-reviewed manuscripts and 31 congress abstracts, and assessed existing guidance and measures of asthma control used in clinical trials. In this publication, we provide further insight into the predefined keywords, search strings, and strategy applied to identify manuscripts and congress abstracts for inclusion/exclusion, and detail methods for data extraction. Together, the data from the Delphi survey and structured literature review aimed to provide greater insights into challenges and approaches in achieving asthma control in clinical practice, with the potential for results to be used to guide a universally accepted definition and measure of asthma control that can be used and understood by patients, HCPs, and researchers. Qualitative and quantitative methodology and analysis from the Delphi survey and literature review search strategy can potentially be used to identify disparities and explore expert opinion and relevant literature in other therapeutic areas to guide a consensus where disparities exist.

Respiratory inhalers and the environment.

BACKGROUND: Several million inhalers are used annually by the millions of Australians with respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD). Prescriptions in primary care tend to be for pressurised metered-dose inhalers (pMDIs), and consumers can purchase pMDI salbutamol over the counter. These inhalers contain potent greenhouse gases. OBJECTIVE: This article briefly summarises the scale of the problem caused by pMDI propellants before discussing options available to general practitioners to mitigate their environmental impact while maintaining high-quality patient care. DISCUSSION: The best inhaler for any patient is one that they can and will use as prescribed. However, for many people with chronic airways diseases, the environmental impact of their inhalers can be considered when doctors make prescribing choices, at least until newer, more climate-friendly propellants are introduced. Other aspects of asthma and COPD management that minimise environmental impact are also important.

Is asthma control more than just an absence of symptoms? An expert consensus statement.

PURPOSE: Definitions and measures of asthma control used in clinical trials and in clinical practice vary considerably. There is also misalignment between patients and healthcare professionals (HCPs) in terms of understanding and managing asthma control. This study aimed to progress towards a consensus definition of asthma control, and evaluate disparities between HCP and patient perspectives. BASIC PROCEDURES: A two-stage Delphi questionnaire involving asthma specialists sought to identify areas of consensus on aspects of asthma control in clinical practice. Results were compared with those of a structured literature review to assess if existing guidance and measures of asthma control used in studies correlated with practice. Eighty-two panelists took part in the Delphi questionnaire. The structured literature review included 185 manuscripts and 31 abstracts. MAIN FINDINGS: Panelists agreed that there was no standard definition of asthma control, confirmed by a total of 19 different composite consensus/guideline definitions and/or validated measures of control being identified across the Delphi study and literature review. Panelists agreed on the positive associations of well-controlled asthma with patient outcomes, but not on the components or thresholds of a working definition of control. PRINCIPAL CONCLUSIONS: A universally accepted definition and measure of asthma control that is utilized and understood by patients, HCPs, and researchers is required.

Characterisation of the Australian Adult Population Living with Asthma: Severe - Exacerbation Frequency, Long-Term OCS Use and Adverse Effects.

Introduction: Asthma poses a significant burden for the Australian population. Understanding severe exacerbation rates, and steroid-related burden for adults diagnosed with asthma stands to offer insights into how this could be reduced. Methods: Electronic medical records (EMR) and questionnaires from the Optimum Patient Care Research Database Australia (OPCRDA) were utilised retrospectively. OPCRDA is a real-world database with >800,000 medical records from Australian primary care practices. Outcomes were severe asthma exacerbations in Australian adults, over a 12-month period, stratified by Global Initiative for Asthma (GINA) treatment intensity steps, and steroid associated comorbidities. Results: Of the 7868 adults treated for asthma, 19% experienced at least one severe exacerbation in the last 12-months. Severe exacerbation frequency increased with treatment intensity (≥1 severe exacerbation GINA 1 13%; GINA 4 23%; GINA 5a 33% and GINA 5b 28%). Questionnaire participants reported higher rates of severe exacerbations than suggested from their EMR (32% vs 23%) especially in steps 1, 4 and 5. Patients repeatedly exposed to steroids had an increased risk of osteoporosis (OR 1.95, 95% CI 1.43-2.66) and sleep apnoea (OR 1.78, 95% CI 1.30-2.46). Conclusion: The Australian population living with GINA 1, 4, 5a and 5b asthma have high severe exacerbation rates and steroid-related burden, especially when compared to other first world countries, with these patients needing alternative strategies or possibly specialist assessment to better manage their condition.

Caregivers' and healthcare professionals' perspective of barriers and facilitators to health service access for asthmatic children: a qualitative study.

BACKGROUND: There is a high burden of asthma morbidity and mortality in Latin America. It has been proposed that this relates to limited access to diagnostic tests, asthma medications and specialised doctors. However, little is known of what caregivers of asthmatic children and healthcare professionals (HCPs) perceive as barriers and facilitators to adequate care. We aimed to explore the barriers and facilitators to asthma care access from caregivers' and HCP's perspective in an Ecuadorian low-resource setting. METHODS: In 2017, we conducted 5 focus group discussions (FGD) with 20 caregivers of asthmatic children and 12 in-depth interviews with 3 paediatricians, 6 general doctors and 3 respiratory therapists in Esmeraldas city, Ecuador. FGDs and interviews were digitally recorded, transcribed, open-coded in QDA Miner, categorised using an interpretative phenomenological approach and analysed thematically. Barriers and facilitators were classified into availability, accessibility, acceptability and contact of healthcare services, based on Tanahashi model of health service access. RESULTS: Limited resources, use of alternative medicines, fear of medication side-effects and lack of specific training for doctors and knowledge in families were common barriers for both caregivers and HCPs. Caregivers and HCPs proposed the implementation of public health asthma-focused programmes that would include close community-based follow-up of people with asthma, educational sessions for their families and public engagement activities. HCPs also suggested implementing training programmes on asthma management for general doctors. CONCLUSION: Multiple barriers identified by caregivers and HCPs referred to economic and health service organisational issues, fear of side effects of medication or ineffective self-management. Increasing caregivers and HCPs' asthma knowledge, as well as HCPs' communication skills to establish a patient-centred approach with a shared decision-making process could improve asthma care in this setting.

Oral corticosteroids stewardship for asthma in adults and adolescents: A position paper from the Thoracic Society of Australia and New Zealand.

Oral corticosteroids (OCS) are frequently used for asthma treatment. This medication is highly effective for both acute and chronic diseases, but evidence indicates that indiscriminate OCS use is common, posing a risk of serious side effects and irreversible harm. There is now an urgent need to introduce OCS stewardship approaches, akin to successful initiatives that optimized appropriate antibiotic usage. The aim of this TSANZ (Thoracic Society of Australia and New Zealand) position paper is to review current knowledge pertaining to OCS use in asthma and then delineate principles of OCS stewardship. Recent evidence indicates overuse and over-reliance on OCS for asthma and that doses >1000 mg prednisolone-equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS-related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add-on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk-benefits of OCS medications, side effects, effective add-on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.

A real-life comparative effectiveness study into the addition of antibiotics to the management of asthma exacerbations in primary care.

BACKGROUND: Asthma exacerbations are major contributors to asthma morbidity and mortality. They are usually managed with bronchodilators and oral corticosteroids (OCS), but clinical trial evidence suggests that antibiotics could be beneficial. We aimed to assess whether treatment of asthma exacerbations with antibiotics in addition to OCS improved outcomes in larger, more representative routine-care populations. METHOD: A retrospective comparative effectiveness study into managing asthma exacerbations with OCS alone versus OCS plus antibiotics was conducted using the Optimum Patient Care Research Database. The dataset included 28 637 patients; following propensity score matching 20 024 adults and 4184 children were analysed. RESULTS: Antibiotics in addition to OCS were prescribed for the treatment of asthma exacerbations in 45% of adults and 32% of children. Compared to OCS alone, OCS plus antibiotics was associated with reduced risk of having an asthma/wheeze consultation in the following 2 weeks (children hazard ratio (HR) 0.84 (95% CI 0.73-0.96), p=0.012; adults HR 0.86 (95% CI 0.81-0.91), p<0.001), but an increase in risk of a further OCS prescription for a new/ongoing exacerbation within 6 weeks in adults (HR 1.11 (95% CI 1.01-1.21), p=0.030), but not children. Penicillins, but not macrolides, were associated with a reduction in the odds of a subsequent asthma/wheeze consultation compared to OCS alone, in both adults and children. CONCLUSION: Antibiotics were frequently prescribed in relation to asthma exacerbations, contrary to guideline recommendations. Overall, the routine addition of antibiotics to OCS in the management of asthma exacerbations appeared to confer little clinical benefit, especially when considering the risks of antibiotic overuse.

The Effect of Connected "Smart" Inhalers on Medication Adherence.

Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent worldwide, and major sources of morbidity. Key barriers to reduce the harm from these conditions are the widespread and related issues of low use of prescribed inhaled therapy, use of medicines differently from that prescribed, suboptimal inhaler technique, and lack of adherence are the action plans. Connected smart inhalers show great potential to improve these issues, and thus outcomes from airways disease. In this mini-review, we considered the published evidence that the use of smart inhalers leads to more doses of preventative treatment being taken on time and with appropriate techniques. We found multiple trials across a variety of settings and age groups where smart inhalers were used with audio-visual reminders and healthcare professional feedback, which substantially improved the number of doses of preventative treatment taken. Trial evidence also supports the use of feedback from smart inhalers in improving true concordance (doses taken correctly and on time), though only for a single type of smart device. The relative lack of study is in contrast with the potential impact of smart inhalers. Major research questions remain unresolved, as who might fund future large-scale studies, how guideline committees may consider them, and how to implement effective solutions.

Phenotypic and functional translation of IL33 genetics in asthma.

BACKGROUND: Asthma is a complex disease with multiple phenotypes that may differ in disease pathobiology and treatment response. IL33 single nucleotide polymorphisms (SNPs) have been reproducibly associated with asthma. IL33 levels are elevated in sputum and bronchial biopsies of patients with asthma. The functional consequences of IL33 asthma SNPs remain unknown. OBJECTIVE: This study sought to determine whether IL33 SNPs associate with asthma-related phenotypes and with IL33 expression in lung or bronchial epithelium. This study investigated the effect of increased IL33 expression on human bronchial epithelial cell (HBEC) function. METHODS: Association between IL33 SNPs (Chr9: 5,815,786-6,657,983) and asthma phenotypes (Lifelines/DAG [Dutch Asthma GWAS]/GASP [Genetics of Asthma Severity & Phenotypes] cohorts) and between SNPs and expression (lung tissue, bronchial brushes, HBECs) was done using regression modeling. Lentiviral overexpression was used to study IL33 effects on HBECs. RESULTS: We found that 161 SNPs spanning the IL33 region associated with 1 or more asthma phenotypes after correction for multiple testing. We report a main independent signal tagged by rs992969 associating with blood eosinophil levels, asthma, and eosinophilic asthma. A second, independent signal tagged by rs4008366 presented modest association with eosinophilic asthma. Neither signal associated with FEV1, FEV1/forced vital capacity, atopy, and age of asthma onset. The 2 IL33 signals are expression quantitative loci in bronchial brushes and cultured HBECs, but not in lung tissue. IL33 overexpression in vitro resulted in reduced viability and reactive oxygen species-capturing of HBECs, without influencing epithelial cell count, metabolic activity, or barrier function. CONCLUSIONS: We identify IL33 as an epithelial susceptibility gene for eosinophilia and asthma, provide mechanistic insight, and implicate targeting of the IL33 pathway specifically in eosinophilic asthma.

Phenotypic and functional translation of IL1RL1 locus polymorphisms in lung tissue and asthmatic airway epithelium.

The IL1RL1 (ST2) gene locus is robustly associated with asthma; however, the contribution of single nucleotide polymorphisms (SNPs) in this locus to specific asthma subtypes and the functional mechanisms underlying these associations remain to be defined. We tested for association between IL1RL1 region SNPs and characteristics of asthma as defined by clinical and immunological measures and addressed functional effects of these genetic variants in lung tissue and airway epithelium. Utilizing 4 independent cohorts (Lifelines, Dutch Asthma GWAS [DAG], Genetics of Asthma Severity and Phenotypes [GASP], and Manchester Asthma and Allergy Study [MAAS]) and resequencing data, we identified 3 key signals associated with asthma features. Investigations in lung tissue and primary bronchial epithelial cells identified context-dependent relationships between the signals and IL1RL1 mRNA and soluble protein expression. This was also observed for asthma-associated IL1RL1 nonsynonymous coding TIR domain SNPs. Bronchial epithelial cell cultures from asthma patients, exposed to exacerbation-relevant stimulations, revealed modulatory effects for all 4 signals on IL1RL1 mRNA and/or protein expression, suggesting SNP-environment interactions. The IL1RL1 TIR signaling domain haplotype affected IL-33-driven NF-κB signaling, while not interfering with TLR signaling. In summary, we identify that IL1RL1 genetic signals potentially contribute to severe and eosinophilic phenotypes in asthma, as well as provide initial mechanistic insight, including genetic regulation of IL1RL1 isoform expression and receptor signaling.

A systematic review of methodology used in the development of prediction models for future asthma exacerbation.

BACKGROUND: Clinical prediction models are widely used to guide medical advice and therapeutic interventions. Asthma is one of the most common chronic diseases globally and is characterised by acute deteriorations. These exacerbations are largely preventable, so there is interest in using clinical prediction models in this area. The objective of this review was to identify studies which have developed such models, determine whether consistent and appropriate methodology was used and whether statistically reliable prognostic models exist. METHODS: We searched online databases MEDLINE (1948 onwards), CINAHL Plus (1937 onwards), The Cochrane Library, Web of Science (1898 onwards) and ClinicalTrials.gov, using index terms relating to asthma and prognosis. Data was extracted and assessment of quality was based on GRADE and an early version of PROBAST (Prediction study Risk of Bias Assessment Tool). A meta-analysis of the discrimination and calibration measures was carried out to determine overall performance across models. RESULTS: Ten unique prognostic models were identified. GRADE identified moderate risk of bias in two of the studies, but more detailed quality assessment via PROBAST highlighted that most models were developed using highly selected and small datasets, incompletely recorded predictors and outcomes, and incomplete methodology. None of the identified models modelled recurrent exacerbations, instead favouring either presence/absence of an event, or time to first or specified event. Preferred methodologies were logistic regression and Cox proportional hazards regression. The overall pooled c-statistic was 0.77 (95% confidence interval 0.73 to 0.80), though individually some models performed no better than chance. The meta-analysis had an I2 value of 99.75% indicating a high amount of heterogeneity between studies. The majority of studies were small and did not include internal or external validation, therefore the individual performance measures are likely to be optimistic. CONCLUSIONS: Current prognostic models for asthma exacerbations are heterogeneous in methodology, but reported c-statistics suggest a clinically useful model could be created. Studies were consistent in lacking robust validation and in not modelling serial events. Further research is required with respect to incorporating recurrent events, and to externally validate tools in large representative populations to demonstrate the generalizability of published results.

Antibiotics for COPD exacerbations: does drug or duration matter? A primary care database analysis.

Introduction: Antibiotics are routinely given to people with chronic obstructive pulmonary disease (COPD) presenting with lower respiratory tract infection (LRTI) symptoms in primary care. Population prescribing habits and their consequences have not been well-described. Methods: We conducted a retrospective analysis of antibiotic prescriptions for non-pneumonic exacerbations of COPD from 2010 to 2015 using the UK primary care Optimum Patient Care Research Database. As a proxy of initial treatment failure, second antibiotic prescriptions for LRTI or all indications within 14 days were the primary and secondary outcomes, respectively. We derived a model for repeat courses using univariable and multivariable logistic regression analysis. Results: A total of 8.4% of the 9042 incident events received further antibiotics for LRTI, 15.5% further courses for any indication. Amoxicillin and doxycycline were the most common index and second-line drugs, respectively (58.7% and 28.7%), mostly given for 7 days. Index drugs other than amoxicillin, cardiovascular disease, pneumococcal vaccination and more primary care consultations were statistically significantly associated with repeat prescriptions for LRTI (p<0.05). The ORs and 95% CIs were: OR 1.28, 95% CI 1.10 to 1.49; OR 1.37, 95% CI 1.13 to 1.66; OR 1.33, 95% CI 1.14 to 1.55 and OR 1.05, 95% CI 1.02 to 1.07, respectively. Index duration, inhaled steroid use and exacerbation frequency were not statistically significant. The derived model had an area under the curve of 0.61, 95% CI 0.59 to 0.63. Discussion: The prescription of multiple antibiotic courses for COPD exacerbations was relatively common-one in twelve patients receiving antibiotics for LRTI had a further course within 2 weeks. The findings support the current preference for amoxicillin as index drug within the limitations of this observational study. Further clinical trials to determine best practice in this common clinical situation appear required.

Observational cohort study to investigate the unmet need and time waiting for referral for specialist opinion in adult asthma in England (UNTWIST asthma).

OBJECTIVES: This study aimed to estimate how many patients with asthma in England met the referral eligibility criteria using national asthma guidelines, identify what proportion were referred and determine the average waiting time to referral. DESIGN: This is an observational cohort study. SETTING/DATA SOURCES: Routinely collected healthcare data were provided by Clinical Practice Research Datalink records and Hospital Episode Statistics records from January 2007 to December 2015. PARTICIPANTS: Patients with asthma aged 18-80 years participated in this study. MAIN OUTCOME MEASURES: Eligibility for referral by the British Thoracic Society/Scottish Intercollegiate Guidelines Network (BTS/SIGN) 2016 guidelines, determined after a 3-month pharmacological therapy exposure assessment, was classed by either 'high-dose therapies', 'continuous or frequent use of oral steroids' or 'incident eligibility' during follow-up (continuous oral corticosteroids for more than 3 months, or ≥800 µg/day inhaled corticosteroids/long-acting ß2-agonist (or three controllers) and ≥2 asthma attacks/year). RESULTS: From the final cohort (n=23293), 19837 patients were eligible for specialist referral during follow-up based on the BTS/SIGN guideline recommendations. Among eligible patients without any previously recorded referral, 4% were referred during follow-up, with a median waiting time of 880 days (IQR=1428 days) between eligibility and referral. CONCLUSIONS: A large number of patients with asthma were eligible for specialist referral, of which a small proportion were referred, and many experienced a long waiting time before referral. The results indicate a major unmet need in asthma referral, which is a potential source of preventable harm and are likely to have implications regarding how services are organised to address this unmet need.