Respiratory
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Research outputs from the Respiratory Medicine department at the RD&E.
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Item Personalizing Selection of Inhaled Delivery Systems in COPD(American Thoracic Society, 2023-07-01) Mahler, D. A.; Halpin, D. M. G.It can be challenging for health care professionals (HCPs) to prescribe inhaled therapy for patients with chronic obstructive pulmonary disease (COPD) due to the multiple individual and combinations of inhaled medications available in numerous delivery systems. Guidance on selection of an inhaled delivery system has received limited attention compared with the emphasis on prescribing the class of the inhaled molecule(s). Although numerous recommendations and algorithms have been proposed to guide selection of an inhaled delivery system for patients with COPD, no specific approach has been endorsed in COPD guidelines/strategies or by professional organizations. To provide recommendations for an inhaler selection strategy at initial and follow-up appointments, we examined the impact of patient errors using hand held inhalers on clinical outcomes and performed a focused narrative review to consider patient factors (continuity of the inhaled delivery system, cognitive function, manual function/dexterity, and peak inspiratory flow) when selecting an inhaled delivery system. Based on these findings, five questions are proposed for HCPs to consider in the initial selection of an inhaler delivery system and three questions to consider at follow-up. We propose that HCPs consider the inhaled medication-delivery system as a unit and to match an appropriate medication(s) with the unique features of the delivery system to individual patient factors. Assessment of inhaler technique and adherence along with patient outcomes/satisfaction at each visit is essential to determine whether the inhaled medication-delivery system is providing benefits. Continued and repeated education on device features and correct technique is warranted to optimize efficacy.Item Do the 'missing millions' of COPD patients want to be found?(BMJ, 2023-03-27) Halpin, D. M.Item Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosis(Elsevier, 2023-01-01) Mikolasch, T. A.; George, P. M.; Sahota, J.; Nancarrow, T.; Barratt, S. L.; Woodhead, F. A.; Kouranos, V.; Cope, V. S. A.; Creamer, A. W.; Fidan, S.; Ganeshan, B.; Hoy, L.; Mackintosh, J. A.; Shortman, R.; Duckworth, A.; Fallon, J.; Garthwaite, H.; Heightman, M.; Adamali, H. I.; Lines, S.; Win, T.; Wollerton, R.; Renzoni, E. A.; Steward, M.; Wells, A. U.; Gibbons, M.; Groves, A. M.; Gooptu, B.; Scotton, C. J.; Porter, J. C.BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in IPF. METHODS: We adopted a two-stage discovery (n = 71) and validation (n = 134) design using patients from the UCL partners (UCLp) cohort. We then combined discovery and validation cohorts and included an additional 794 people with IPF, using real-life data from 5 other UK centers, to give a combined cohort of 999 patients. Data were collected from patients presenting over a 13-year period (2006-2019) with mean follow up of 3.7 years (censoring: 2018-2020). FINDINGS: In the discovery analysis, we showed that high values of NLR (>/ = 2.9 vs < 2.9) were associated with increased risk of mortality in IPF (HR 2.04, 95% CI 1.09-3.81, n = 71, p = 0.025). This was confirmed in the validation (HR 1.91, 95% CI 1.15-3.18, n = 134, p = 0.0114) and combined cohorts (HR 1.65, n = 999, 95% CI 1.39-1.95; p < 0·0001). NLR correlated with GAP stage and GAP index (p < 0.0001). Stratifying patients by NLR category (low/high) showed significant differences in survival for GAP stage 2 (p < 0.0001), however not for GAP stage 1 or 3. In a multivariate analysis, a high NLR was an independent predictor of mortality/progression after adjustment for individual GAP components and steroid/anti-fibrotic use (p < 0·03). Furthermore, incorporation of baseline NLR in a modified GAP-stage/index, GAP-index/stage-plus, refined prognostic ability as measured by concordance (C)-index. INTERPRETATION: We have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines cohort staging with GAP. NLR may allow timely prioritisation of at-risk patients, even in the absence of lung function. FUNDING: Breathing Matters, GSK, CF Trust, BLF-Asthma, MRC, NIHR Alpha-1 Foundation.Item Nintedanib for non-IPF progressive pulmonary fibrosis: 12-month outcome data from a real-world multicentre observational study(European Respiratory Society, 2023-03-01) Raman, L.; Stewart, I.; Barratt, S. L.; Chua, F.; Chaudhuri, N.; Crawshaw, A.; Gibbons, M.; Hogben, C.; Hoyles, R.; Kouranos, V.; Martinovic, J.; Mulholland, S.; Myall, K. J.; Naqvi, M.; Renzoni, E. A.; Saunders, P.; Steward, M.; Suresh, D.; Thillai, M.; Wells, A. U.; West, A.; Mitchell, J. A.; George, P. M.BACKGROUND: Nintedanib slows lung function decline for patients with non-idiopathic pulmonary fibrosis progressive pulmonary fibrosis (PPF) in clinical trials, but the real-world safety and efficacy are not known. METHODS: In this retrospective cohort study, standardised data were collected from patients in whom nintedanib was initiated for PPF between 2019 and 2020 through an early-access programme across eight centres in the United Kingdom. Rate of lung function change in the 12 months pre- and post-nintedanib initiation was the primary analysis. Symptoms, drug safety, tolerability and stratification by interstitial lung disease subtype and computed tomography pattern were secondary analyses. RESULTS: 126 patients were included; 67 (53%) females; mean±sd age 60±13 years. At initiation of nintedanib, mean forced vital capacity (FVC) was 1.87 L (58% predicted) and diffusing capacity of the lung for carbon monoxide (D (LCO)) was 32.7% predicted. 68% of patients were prescribed prednisolone (median dose 10 mg) and 69% were prescribed a steroid-sparing agent. In the 12 months after nintedanib initiation, lung function decline was significantly lower than in the preceding 12 months: FVC -88.8 mL versus -239.9 mL (p=0.004), and absolute decline in D (LCO) -2.1% versus -6.1% (p=0.004). Response to nintedanib was consistent in sensitivity and secondary analyses. 89 (71%) out of 126 patients reported side-effects, but 86 (80%) of the surviving 108 patients were still taking nintedanib at 12 months with patients reporting a reduced perception of symptom decline. There were no serious adverse events. CONCLUSION: In PPF, the real-world efficacy of nintedanib replicated that of clinical trials, significantly attenuating lung function decline. Despite the severity of disease, nintedanib was safe and well tolerated in this real-world multicentre study.Item Moving towards patient-centred outcomes: the Severe Asthma Questionnaire(European Respiratory Society, 2022-12-30) Davies, D.; Hyland, M. E.; Lanario, J. W.; Jones, R. C.; Masoli, M.