Publications
242 results found
Garner J, Biddiscombe MF, Meah S, et al., 2021, Endobronchial Valve Lung Volume Reduction and Small Airways Function., Am J Respir Crit Care Med
Biddiscombe M, Usmani O, 2021, Delivery and adherence with inhaled therapy in asthma., Minerva Med
The benefits of inhaled medication for the treatment of respiratory diseases are immense. Inhalers are unquestionably the most important medical devices for the treatment of asthma and in Europe today there are more than 230 different device and drug combinations of inhaled therapies many of which are available for the treatment of asthma. They are designed to alleviate the symptoms of asthma by controlling inflammation and minimising exacerbations and are intended to be simple enough to operate by all patients regardless of their age and education. However, it is still a huge challenge for patients to use their inhaler correctly and consistently and achieving asthma control continues to be an elusive goal for most patients worldwide. The reality is that despite advances in the diagnosis of asthma, the availability of comprehensive asthma management guidelines and potent asthma medications combined with efficient delivery systems, uncontrolled disease is still linked to substantial morbidity and mortality. Despite the enormous benefits of delivering topically acting medication directly to the site of disease in the lungs adherence to treatment still remains one of the biggest challenges in asthma control. This current review looks at why patients have difficulty in using their inhalers and why adherence is so poor and how this may be improved through the use of innovation in inhaler design.
Bousquet J, Anto JM, Bachert C, et al., 2021, ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice., Allergy, Vol: 76, Pages: 168-190, ISSN: 0105-4538
Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis.It strengthens the ARIA change management strategy in the prevention and managementof airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
Dreher M, Price D, Gardev A, et al., 2021, Patient perceptions of the re-usable Respimatt® Soft Mist™ inhaler in current users and those switching to the device: A real-world, non-interventional COPD study., Chron Respir Dis, Vol: 18
PLAIN LANGUAGE SUMMARY: Inhalers are often used to treat patients with chronic obstructive pulmonary disease (COPD). However, there are many available, which can lead to confusion and poor inhaler technique. It is important for a patient to be happy with their inhaler. This study looked at how patients liked the re-usable Respimat® Soft Mist™ inhaler vs. their previous inhaler. It also asked whether they would be willing to continue using the device at the end of the study period.After 4-6 weeks of using the re-usable device, patients reported that they were happy with the inhaler and most would be willing to carry on using it.Overall, these results show that doctors can prescribe Respimat re-usable to patients, even if the patient has not used the inhaler before.
Pleasants RA, Tilley SL, Hickey AJ, et al., 2021, User-life of ICS/LABA inhaler devices should be considered when prescribed as relievers., Eur Respir J, Vol: 57
Usmani OS, Roche N, Jenkins M, et al., 2021, Consistent Pulmonary Drug Delivery with Whole Lung Deposition Using the Aerosphere Inhaler: A Review of the Evidence, The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 16, Pages: 113-124, ISSN: 1176-9106
Metered dose inhalers (MDIs) are one of the most common device types for delivering inhaled therapies. However, there are several technical challenges in development and drug delivery of these medications. In particular, suspension-based MDIs are susceptible to suspension heterogeneity, in vitro drug-drug interactions, and patient handling errors, which may all affect drug delivery. To overcome these challenges, new formulation approaches are required. The AerosphereTM inhaler, formulated using co-suspension delivery technology, combines drug crystals with porous phospholipid particles to create stable, homogenous suspensions that dissolve once they reach the airways. Two combination therapies using this technology have been developed for the treatment of COPD: glycopyrrolate/formoterol fumarate (GFF MDI; dual combination) and budesonide/glycopyrrolate/formoterol fumarate (BGF MDI; triple combination). Here, we review the evidence with a focus on studies assessing dose delivery, lung deposition, and effects on airway geometry. In vitro assessments have demonstrated that the Aerosphere inhaler provides consistent dose delivery, even in the presence of simulated patient handling errors. Combination therapies delivered with this technology also show a consistent fine particle fraction (FPF) and an optimal particle size distribution for delivery to the central and peripheral airways even when multiple drugs are delivered via the same inhaler. Studies using gamma scintigraphy and functional respiratory imaging have demonstrated that GFF MDI is effectively deposited in the central and peripheral airways, and provides clinically meaningful benefits on airway volume and resistance throughout the lung. Overall, studies suggest that the Aerosphere inhaler, formulated using co-suspension delivery technology, may offer advantages over traditional formulations, including consistent delivery of multiple components across patient handling conditions, optimal particle size and FPF
Alzahabi KH, Usmani O, Georgiou TK, et al., 2020, Approaches to treating tuberculosis by encapsulating metal ions and anti-mycobacterial drugs utilizing nano- and microparticle technologies, EMERGING TOPICS IN LIFE SCIENCES, Vol: 4, Pages: 581-600, ISSN: 2397-8554
Soni S, Garner J, O'Dea K, et al., 2020, Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD, American Journal of Physiology: Lung Cellular and Molecular Physiology, ISSN: 1040-0605
Despite advances in the pathophysiology of Chronic Obstructive Pulmonary Disease (COPD), there is a distinct lack of biochemical markers to aid clinical management. Microvesicles (MVs) have been implicated in the pathophysiology of inflammatory diseases including COPD but their association to COPD disease severity remains unknown. We analysed different MV populations in plasma and bronchoalveolar lavage fluid (BALF) taken from sixty-two patients with mild to very severe COPD (51% male; mean age: 65.9 years). These patients underwent comprehensive clinical evaluation (symptom scores, lung function, exercise testing) and the capacity of MVs to be clinical markers of disease severity was assessed. We successfully identified various MV subtype populations within BALF (leukocyte, PMN (polymorphonuclear leukocyte i.e. neutrophil), monocyte, epithelial and platelet MVs) and plasma (leukocyte, PMN, monocyte and endothelial MVs), and compared each MV population to disease severity. BALF neutrophil MVs were the only population to significantly correlate with the clinical evaluation scores including FEV1, mMRC dyspnoea score, 6-minute walk test, hyperinflation and gas transfer. BALF neutrophil MVs, but not neutrophil cell numbers, also strongly correlated with BODE index. We have undertaken, for the first time, a comprehensive evaluation of MV profiles within BALF/plasma of COPD patients. We demonstrate that BALF levels of neutrophil-derived MVs are unique in correlating with a number of key functional and clinically-relevant disease severity indices. Our results show the potential of BALF neutrophil MVs for a COPD biomarker that tightly links a key pathophysiological mechanism of COPD (intra-alveolar neutrophil activation) with clinical severity/outcome.
Soriano JB, Anzueto A, Anticevich SB, et al., 2020, Face masks, respiratory patients and COVID-19, European Respiratory Journal, Vol: 56, ISSN: 0903-1936
Usmani OS, Mignot B, Kendall I, et al., 2020, Predicting Lung Deposition of Extrafine Inhaled Corticosteroid-Containing Fixed Combinations in Patients with Chronic Obstructive Pulmonary Disease Using Functional Respiratory Imaging: AnIn SilicoStudy, JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY, ISSN: 1941-2711
Stanford G, Davies JC, Usmani O, et al., 2020, Investigating outcome measures for assessing airway clearance techniques in adults with cystic fibrosis: protocol of a single-centre randomised controlled crossover trial, BMJ Open Respiratory Research, Vol: 7, ISSN: 2052-4439
INTRODUCTION: Airway clearance techniques (ACTs) are a gold standard of cystic fibrosis management; however, the majority of research evidence for their efficacy is of low standard; often attributed to the lack of sensitivity from outcome measures (OMs) used historically. This randomised controlled trial (RCT) investigates these standard OMs (sputum weight, forced expiratory volume in 1 s) and new OMs (electrical impedance tomography (EIT), multiple breath washout (MBW) and impulse oscillometry (IOS)) to determine the most useful measures of ACT. METHODS AND ANALYSIS: This is a single-centre RCT with crossover design. Participants perform MBW, IOS and spirometry, and then are randomised to either rest or supervised ACT lasting 30-60 min. MBW, IOS and spirometry are repeated immediately afterwards. EIT and sputum are collected during rest/ACT. On a separate day, the OMs are performed with the other intervention. Primary endpoint is difference in change in OMs before and after ACT/rest. Sample size was calculated with 80% power and significance of 5% for each OM (target n=64). ETHICS AND DISSEMINATION: Ethics approval was gained from the London-Chelsea Research Ethics Committee (reference 16/LO/0995, project ID 154635). Dissemination will involve scientific conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ISRCTN11220163 and NCT02721498.
Usmani O, Roche N, Abd Wahab E, et al., 2020, A SCINTIGRAPHY STUDY OF BUDESONIDE/GLYCOPYRROLATE/FORMOTEROL FUMARATE IN PATIENTS WITH COPD, Annual Meeting of the American-College-of-Chest-Physicians (CHEST), Publisher: ELSEVIER, Pages: 2435A-2437A, ISSN: 0012-3692
Baldi S, Usmani O, Van Holsbeke C, et al., 2020, EFFECT OF SWITCHING FROM MULTI-INHALER NON-EXTRA FINE TO SINGLE-INHALER EXTRA FINE TRIPLE THERAPHY ON REGIONAL BRONCHODILATION AND VENTILATION IN PATIENTS WITH SEVERE COPD, Annual Meeting of the American-College-of-Chest-Physicians (CHEST), Publisher: ELSEVIER, Pages: 1664A-1665A, ISSN: 0012-3692
Kerkhof M, Chaudhry I, Pavord ID, et al., 2020, Blood eosinophil count predicts treatment failure and hospital readmission for COPD, ERJ OPEN RESEARCH, Vol: 6
Bonini M, Cilluffo G, La Grutta S, et al., 2020, Anti-muscarinic drugs as preventive treatment of exercise-induced bronchoconstriction (EIB) in children and adults, RESPIRATORY MEDICINE, Vol: 172, ISSN: 0954-6111
Haughney J, Lee AJ, McKnight E, et al., 2020, Peak inspiratory flow measured at different inhaler resistances in patients with asthma, Journal of Allergy and Clinical Immunology: In Practice, ISSN: 2213-2198
BACKGROUND: Patients' peak inspiratory flow rate (PIFR) may help clinicians select an inhaler device. OBJECTIVE: To determine the proportion of patients with asthma who could generate correct PIFRs at different inhaler resistance settings. METHODS: During a UK asthma review service, patients' PIFR was checked at resistance settings matching their current preventer inhaler device, at R5 (high resistance dry powder inhaler (DPI)) and at R0 (low resistance, pressurised metered dose inhaler (pMDI)). Correct PIFR ('pass') was defined for R5 as 30-90 L/min and for R0 as 20-60 L/min. A logistic regression model examined the independent predictors of incorrect PIFR ('fail') at R5 and R0. Asthma severity was assessed retrospectively from treatment level. RESULTS: A total of 994 adults (female 64.3%) were included, of whom 90.4% currently used a preventer inhaler (71.5% pMDI). PIFR pass rates were: 93.7% at R5 compared with 70.5% at R0 (p<0.0001). All patients failing the R0 PIFR breathed in too fast (>60 L/min), and 20% of patients currently using pMDI failed for this reason. Independent risk factors for failing R5 were: female gender, older age group and current preventer pMDI; and for failing R0 included: male gender, younger age group, current preventer DPI and mild versus severe asthma. CONCLUSIONS: This study demonstrates that most patients with asthma can achieve adequate inspiratory flow to activate high resistance DPIs, whereas approximately a third of patients breathe in too fast to achieve recommended inspiratory flows for correct pMDI use, including one fifth of patients who currently use a pMDI preventer.
Israel S, Kumar A, DeAngelis K, et al., 2020, Pulmonary deposition of budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler formulated using co-suspension delivery technology in healthy male subjects, European Journal of Pharmaceutical Sciences, Vol: 153, ISSN: 0928-0987
This gamma scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 μg), delivered by pressurised metered dose inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two actuations of BGF MDI (160/7.2/4.8 μg per actuation) radiolabelled with 99mTc, not exceeding 5 MBq per actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by gamma scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.
Bousquet J, Jutel M, Akdis CA, et al., 2020, ARIA-EAACI statement on asthma and COVID-19 (June 2, 2020), Allergy, ISSN: 0105-4538
Biddiscombe M, Matthews J, Wright M, et al., 2020, No evidence electric charge increases inhaled ultrafine particle deposition in human lungs, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Dreher M, Price D, Gardev A, et al., 2020, Late Breaking Abstract - Switching from a disposable to a re-usable inhaler: patient satisfaction and preference, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Kocks J, Andringa H, Van Heijst E, et al., 2020, The sensitivity and specificity of specific IgE in diagnosing asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Haughney J, Pertsovskaya I, Lee AJ, et al., 2020, Peak inspiratory flow measured at different inhaler resistances in patients with asthma, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Satia I, Nagashima A, Usmani OS, 2020, Exploring the role of nerves in asthma; insights from the study of cough, BIOCHEMICAL PHARMACOLOGY, Vol: 179, ISSN: 0006-2952
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Bakakos A, Loukides S, Usmani OS, et al., 2020, Biologics in severe asthma: the overlap endotype-opportunities and challenges, EXPERT OPINION ON BIOLOGICAL THERAPY, Vol: 20, Pages: 1427-1434, ISSN: 1471-2598
Verbanck S, Biddiscombe MF, Usmani OS, 2020, Inhaled aerosol dose distribution between proximal bronchi and lung periphery, European Journal of Pharmaceutics and Biopharmaceutics, Vol: 152, Pages: 18-22, ISSN: 0939-6411
Modern inhaled drug discovery programs assess dose delivery to proximal and distal airways using rudimentary imaging indices, where relative deposition is estimated by generically defined 'central' and 'peripheral' lung regions. Utilizing recent data linking the proximal airway topology to a characteristic pattern of aerosol lung deposition, we provide a direct measure of dose distribution between the proximal bronchi and the distal lung. We analyzed scintigraphic lung images of twelve asthma patients following inhalation of 1.5-, 3- and 6-µm monodisperse drug particles at breathing flows of 30- and 60-L/min. We explicitly used the central hot-spots associated with each patient's specific bronchial topology to obtain a direct measure of aerosol deposition in the proximal bronchi, rather than applying standard templates of lung boundaries. Maximum deposition in the central bronchi (as % of lung deposition) was 52±10(SD)% (6µm;60L/min). Minimum central deposition was 17±2(SD)% (1.5µm;30L/min) where the 83% aerosol 'escaping' deposition in the central bronchi reached 75±17(SD)% of the lung area that could be reached by Krypton gas. For all particle sizes, hot-spots appeared in the same patient-specific central airway location, with greatest intensity at 60L/min. For a range of respirable aerosol sizes and breathing flows, we have quantified deposited dose in the proximal bronchi and their distal lung reach, constituting a platform to support therapeutic inhaled aerosol drug development.
Usmani OS, 2020, Calling Time on Spirometry: Unlocking the Silent Zone in Acute Rejection after Lung Transplantation, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 201, Pages: 1468-1470, ISSN: 1073-449X
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Khusial RJ, Honkoop PJ, Usmani O, et al., 2020, Effectiveness of myAirCoach: A mHealth Self-Management System in Asthma, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE, Vol: 8, Pages: 1972-+, ISSN: 2213-2198
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Usmani OS, Matthews JC, Wright MD, et al., 2020, No evidence electric charge increases inhaled ultrafine particle deposition in human lungs, American Journal of Respiratory and Critical Care Medicine, Vol: 201, Pages: 1301-1303, ISSN: 1073-449X
Moitra S, Moitra S, Ghosh AK, et al., 2020, Reference values of impulse oscillometry (IOS) for healthy Indian adults, INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE, Vol: 24, Pages: 536-539, ISSN: 1027-3719
Bonini M, Usmani OS, 2020, Drugs for airway disease, Medicine (United Kingdom), Vol: 48, Pages: 314-322, ISSN: 1357-3039
© 2020 Asthma is a heterogeneous disease characterized by chronic airway inflammation and variable expiratory airflow limitation. It affects 5–15% of people worldwide and has shown an increasing prevalence over the last decade. The treatment of asthma is well established in current guidelines, with the aim of achieving optimal disease control and preventing acute exacerbations using a stepwise medication approach. Drugs are commonly divided into ‘relievers’, which quickly reverse airway obstruction, and ‘controllers’, which target the underlying inflammation providing long-term control. β2-adrenoceptor agonists are the most effective therapy for preventing and treating bronchial obstruction, while inhaled corticosteroids are recommended as first-line chronic therapy for persistent asthma. Drugs such as muscarinic antagonists, anti-leukotrienes and macrolides also play a role in disease management. New personalized therapies, such as biological agents or small molecules, have become available or are under development for treatment of severe asthma, together presenting opportunities with developments in biomarkers for interventions of precision medicine.
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