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Background: Rare cystic lung diseases are increasingly recognised due the wider application of CT scanning making cystic lung disease management a growing part of respiratory care. Cystic lung diseases tend to have extrapulmonary features that can both be diagnostic but also require surveillance and treatment in their own right. As some of these diseases now have specific treatments, making a precise diagnosis is crucial. While Langerhans cell histiocytosis, Birt-Hogg-Dubé syndrome, lymphoid interstitial pneumonia and lymphangioleiomyomatosis are becoming relatively well-known diseases to respiratory physicians, a targeted and thorough workup improves diagnostic accuracy and may suggest other ultrarare diseases such as light chain deposition disease, cystic pulmonary amyloidosis, low-grade metastatic neoplasms or infections. In many cases, diagnostic information is overlooked leaving uncertainty over the disease course and treatments., Aims: This position statement from the Rare Disease Collaborative Network for cystic lung diseases will review how clinical, radiological and physiological features can be used to differentiate between these diseases., Narrative: We highlight that in many cases a multidisciplinary diagnosis can be made without the need for lung biopsy and discuss where tissue sampling is necessary when non-invasive methods leave diagnostic doubt. We suggest an initial workup focusing on points in the history which identify key disease features, underlying systemic and familial diseases and a clinical examination to search for connective tissue disease and features of genetic causes of lung cysts. All patients should have a CT of the thorax and abdomen to characterise the pattern and burden of lung cysts and extrapulmonary features and also spirometry, gas transfer and a 6 min walk test. Discussion with a rare cystic lung disease centre is suggested before a surgical biopsy is undertaken., Conclusions: We suggest that this focused workup should be performed in all people with multiple lung cysts and would streamline referral pathways, help guide early treatment, management decisions, improve patient experience and reduce overall care costs. It could also potentially catalyse a national research database to describe these less well-understood and unidentified diseases, categorise disease phenotypes and outcomes, potentially leading to better prognostic data and generating a stronger platform to understand specific disease biology., Competing Interests: Competing interests: AGN reports fees from Galapagos, Medical Quantitative Image Analysis, Roche, Boehringer Ingelheim in relation to interstitial lung disease and lecture fees from Boehringer Ingelheim, UpToDate. PMG reports grants and consulting fees from Boehringer Ingelheim; speaker fees from Boehringer Ingelheim, Roche Pharmaceuticals, AstraZeneca and Cipla; meeting support from Boehringer Ingelheim and Roche Pharmaceuticals; and stock options in Brainomix. SRJ reports grants from the Medical Research Council, NIHR, LAM Action and the LAM Foundation, and educational fees from Boehringer Ingelheim. SRD reports educational fees from Boehringer Ingelheim and advisory fees from GlaxoSmithKline and AstraZeneca., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Osteoporosis and fragility fractures are associated with corticosteroids which are the mainstay treatment for asthma; however, these bone comorbidities within asthma need to be better described., Methods: A matched cohort study was conducted using the UK Clinical Practice Research Database (CPRD). Adults with an incident asthma code were identified and matched, with up to four randomly selected people without asthma, by age, sex and practice. Osteoporosis and fragility fracture incidence rates were calculated, and Cox regression was performed comparing hazard rates to the general population. We report the impact of age, sex, glucocorticoids and the risk of specific fractures., Results: Patients with asthma had a higher risk of osteoporosis (adjusted hazard ratio (aHR) 1.18, 95% CI 1.13-1.23) and were 12% (aHR 1.12, 95% CI 1.07-1.16) more likely to sustain fragility fractures than the general population. Age modified the effect of asthma on osteoporosis and fragility fractures, such that the effect was stronger in younger people (p interaction <0.0001). The vertebra (aHR 1.40, 95% CI 1.33-1.48) and forearm/wrist (aHR 1.27, 95% CI 1.22-1.32) were the sites linked with a larger incidence. A dose-response relationship between oral corticosteroids (OCS) and osteoporosis was observed, whereas the risk of fragility fractures increased in those with six or more OCS courses per year. Regular use of inhaled corticosteroids (ICS) increased the risk of both bone conditions., Conclusions: Patients with asthma are more likely to develop osteoporosis or sustain fragility fractures than the general population, with a particular concern in younger people and those more frequently using OCS and ICS., Competing Interests: Conflict of interest: C.V. Chalitsios has nothing to disclose. Conflict of interest: T.M. McKeever has nothing to disclose. Conflict of interest: D.E. Shaw has nothing to disclose., (Copyright ©ERS 2021.)

Background: Inhaled (ICS) and oral (OCS) corticosteroids are used widely in asthma; however, the risk of osteoporosis and fragility fracture (FF) due to corticosteroids in asthma is not well-established., Methods: We conducted two nested case-control studies using linked data from the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) databases. Using an asthma cohort, we separately identified patients with osteoporosis or FF and gender-, age- and practice-matched controls. Conditional logistic regression was used to determine the association between ICS and OCS exposure, and the risk of osteoporosis or FF. The prevalence of patients receiving at least one bisphosphonate was also calculated., Results: There was a dose-response relationship between both cumulative dose and number of OCS/ICS prescriptions within the previous year, and risk of osteoporosis or FF. After adjusting for confounders, people receiving more OCS prescriptions (≥9 vs 0) had a 4.50 (95% CI 3.21 to 6.11) and 2.16 (95% CI 1.56 to 3.32) increased risk of osteoporosis and FF, respectively. For ICS (≥11 vs 0) the ORs were 1.60 (95% CI 1.22 to 2.10) and 1.31 (95% CI 1.02 to 1.68). The cumulative dose had a similar impact, with those receiving more OCS or ICS being at greater risk. The prevalence of patients taking ≥9 OCS and at least one bisphosphonate prescription was just 50.6% and 48.4% for osteoporosis and FF, respectively., Conclusions: The findings suggest that exposure to OCS or ICS is an independent risk factors for bone health in patients with asthma. Steroid administration at the lowest possible level to maintain asthma control is recommended., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Early Warning Scores (EWSs) are used to monitor patients for signs of imminent deterioration. Although used in respiratory disease, EWSs have not been well studied in this population, despite the underlying cardiopulmonary pathophysiology often present. We examined the performance of two scoring systems in patients with respiratory disease., Design: Retrospective cohort analysis of vital signs observations of all patients admitted to a respiratory unit over a 2-year period. Scores were linked to outcome data to establish the performance of the National EWS (NEWS) compared results to a locally adapted EWS., Setting: Nottingham University Hospitals National Health Service Trust respiratory wards. Data were collected from an integrated electronic observation and task allocation system employing a local EWS, also generating mandatory referrals to clinical staff at set scoring thresholds., Outcome Measures: Projected workload, and sensitivity and specificity of the scores in predicting mortality based on outcome within 24 hours of a score being recorded., Results: 8812 individual patient episodes occurred during the study period. Overall, mortality was 5.9%. Applying NEWS retrospectively (vs local EWS) generated an eightfold increase in mandatory escalations, but had higher sensitivity in predicting mortality at the protocol cut points., Conclusions: This study highlights issues surrounding use of scoring systems in patients with respiratory disease. NEWS demonstrated higher sensitivity for predicting death within 24 hours, offset by reduced specificity. The consequent workload generated may compromise the ability of the clinical team to respond to patients needing immediate input. The locally adapted EWS has higher specificity but lower sensitivity. Statistical evaluation suggests this may lead to missed opportunities for intervention, however, this does not account for clinical concern independent of the scores, nor ability to respond to alerts based on workload. Further research into the role of warning scores and the impact of chronic pathophysiology is urgently needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with difficult-to-control asthma consume 50-60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called 'T2-low asthma' and have a minimal response to corticosteroid therapy. Adjustment of corticosteroid treatment using sputum eosinophil counts from induced sputum has demonstrated reduced severe exacerbation rates and optimized corticosteroid dose. However, it has been challenging to move induced sputum into the clinical setting. There is therefore a need to examine novel algorithms to target appropriate levels of corticosteroid treatment in difficult asthma, particularly in T2-low asthmatics. This study examines whether a composite non-invasive biomarker algorithm predicts exacerbation risk in patients with asthma on high-dose inhaled corticosteroids (ICS) (± long-acting beta agonist) treatment, and evaluates the utility of this composite score to facilitate personalized biomarker-specific titration of corticosteroid therapy., Methods/design: Patients recruited to this pragmatic, multi-centre, single-blinded randomised controlled trial are randomly allocated into either a biomarker controlled treatment advisory algorithm or usual care group in a ratio of 4:1. The primary outcome measure is the proportion of patients with any reduction in ICS or oral corticosteroid dose from baseline to week 48. Secondary outcomes include the rate of protocol-defined severe exacerbations per patient per year, time to first severe exacerbation from randomisation, dose of inhaled steroid at the end of the study, cumulative dose of inhaled corticosteroid during the study, proportion of patients on oral corticosteroids at the end of the study, proportion of patients who decline to progress to oral corticosteroids despite composite biomarker score of 2, frequency of hospital admission for asthma, change in the 7-item Asthma Control Questionnaire (ACQ-7), Asthma Quality of Life Questionnaire (AQLQ), forced expiratory volume in 1 s (FEV1), exhaled nitric oxide, blood eosinophil count, and periostin levels from baseline to week 48. Blood will also be taken for whole blood gene expression; serum, plasma, and urine will be stored for validation of additional biomarkers., Discussion: Multi-centre trials present numerous logistical issues that have been addressed to ensure minimal bias and robustness of study conduct., Trial Registration: ClinicalTrials.gov, NCT02717689 . Registered on 16 March 2016.