Imperial College London

Professor Omar Usmani

Faculty of MedicineNational Heart & Lung Institute

Professor of Respiratory Medicine
 
 
 
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Contact

 

+44 (0)20 7351 8051o.usmani

 
 
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Location

 

Asthma LabSouth BlockRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
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256 results found

Kouri A, Dandurand RJ, Usmani OS, Chow C-Wet al., 2021, Exploring the 175-year history of spirometry and the vital lessons it can teach us today, EUROPEAN RESPIRATORY REVIEW, Vol: 30, ISSN: 0905-9180

Journal article

Usmani O, Roche N, Wahab E, Israel S, Jenkins M, Trivedi R, Dorinsky P, Aurivillius Met al., 2021, A scintigraphy study of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler in patients with moderate-to-very severe chronic obstructive pulmonary disease, Respiratory Research, Vol: 22, Pages: 1-12, ISSN: 1465-9921

BackgroundTriple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting β2-agonists (ICS/LAMA/LABA) is recommended for patients with chronic obstructive pulmonary disease (COPD) with continued symptoms or exacerbations, despite treatment with LAMA/LABA or ICS/LABA. The pulmonary, extrathoracic, and regional lung deposition patterns of a radiolabeled ICS/LAMA/LABA triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate (BGF 320/18/9.6 μg), delivered via a single Aerosphere metered dose inhaler (MDI) were previously assessed in healthy volunteers and showed good deposition to the central and peripheral airways (whole lung deposition: 37.7%). Here, we report the findings assessing BGF in patients with moderate-to-very severe COPD.MethodsThis phase I, single-dose, open-label gamma scintigraphy imaging study (NCT03906045) was conducted in patients with moderate-to-very severe COPD. Patients received two actuations of BGF MDI (160/9/4.8 μg per actuation) radiolabeled with technetium‑99‑pertechnetate, not exceeding 5 MBq per actuation. Immediately following each inhalation, patients performed a breath-hold of up to 10 s, then exhaled into an exhalation filter. Gamma scintigraphy imaging of the anterior and posterior views of the lungs and stomach, and a lateral head and neck view, were performed immediately after exhalation. The primary objective of the study was to assess the pulmonary deposition of BGF. Secondary objectives assessed the deposited dose of radiolabeled BGF in the oropharyngeal and stomach regions, on the actuator, and on the exhalation filter in addition to regional airway deposition patterns in the lungs.ResultsThe mean BGF emitted dose deposited in the lungs was 32.1% (standard deviation [SD] 15.6) in patients with moderate-to-very severe COPD, 35.2% (SD 12.8) in patients with moderate COPD, and 28.7% (SD 18.4) in patients with severe/very severe COPD. Overall, the mean normalized outer/inner ra

Journal article

Biddiscombe MF, Usmani OS, 2021, Delivery and adherence with inhaled therapy in asthma, MINERVA MEDICA, Vol: 112, Pages: 564-572, ISSN: 0026-4806

Journal article

Leving M, Wouters H, de la Hoz A, Bosnic-Anticevich S, Dekhuijzen R, Gardev A, Lavorini F, Meijer J, Price D, Rodriguez MR, Tsiligianni I, Usmani O, Wijnsma B, Kocks Jet al., 2021, Impact of PIF, Inhalation Technique and Medication Adherence on Health Status and Exacerbations in COPD: Protocol of a Real-World Observational Study (PIFotal COPD Study), PULMONARY THERAPY, Vol: 7, Pages: 591-606, ISSN: 2364-1754

Journal article

van Boven JFM, Dierick BJH, Usmani OS, 2021, When biology meets behaviour: can medication adherence mask the contribution of pharmacogenetic effects in asthma?, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936

Journal article

Usmani OS, Dhand R, Lavorini F, Price Det al., 2021, Why We Should Target Small Airways Disease in Our Management of Chronic Obstructive Pulmonary Disease, MAYO CLINIC PROCEEDINGS, Vol: 96, Pages: 2448-2463, ISSN: 0025-6196

Journal article

Usmani OS, Hickey AJ, Guranlioglu D, Rawson K, Stjepanovic N, Siddiqui S, Dhand Ret al., 2021, The impact of inhaler device regimen in patients with asthma or COPD, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 3033-3040.e1, ISSN: 2213-2198

Many inhaler devices with varying handling requirements for optimal use are available for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Patients may be prescribed different device types for reliever and maintenance medications, which may lead to confusion and suboptimal device use. We aimed to understand whether simplifying inhaler regimens by employing a single device type in patients who use multiple devices or prescribing a device with which a patient was already experienced could improve clinical and economic outcomes in asthma and COPD management. A targeted literature search was performed and additional articles were identified through hand searching citations within screened publications. A total of 114 articles were included in the final review. Findings suggest that simplifying inhaler regimens by applying the same type of inhaler for concomitant inhaled medications over time minimizes device misuse, leading to improved clinical outcomes and reduced health care use in patients with asthma or COPD. Physicians should consider a patient's suitability for a device and training needs when prescribing an inhaled medication and before changing the medication type or dose, especially when suboptimal treatment outcomes are observed. Further research is required to determine whether consistent use of the same device type is associated with better treatment adherence and persistence in patients with asthma or COPD. Nevertheless, this literature review identified clinical benefits and reduced health care use with simplified inhaler regimens.

Journal article

Lavorini F, Usmani OS, Dhand R, 2021, Aerosol delivery systems for treating obstructive airway diseases during the SARS-CoV-2 pandemic, INTERNAL AND EMERGENCY MEDICINE, Vol: 16, Pages: 2035-2039, ISSN: 1828-0447

Journal article

Spencer S, Hamer O, Berger E, Booth A, Irving GJ, Owen M, Relph N, Usmani O, Kelly Cet al., 2021, Interventions to improve inhaler technique for adults with chronic obstructive pulmonary disease, Cochrane Database of Systematic Reviews, Vol: 2021, ISSN: 1465-1858

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To evaluate the impact of interventions to improve inhaler technique on performance and clinical outcomes in people with COPD.

Journal article

Usmani OS, Han MK, Kaminsky DA, Hogg J, Hjoberg J, Patel N, Hardin M, Keen C, Rennard S, Ble F-X, Brown MNet al., 2021, Seven Pillars of Small Airways Disease in Asthma and COPD Supporting Opportunities for Novel Therapies, CHEST, Vol: 160, Pages: 114-134, ISSN: 0012-3692

Journal article

Usmani OS, Mignot B, Kendall I, De Maria R, Cocconi D, Georges G, Scichilone Net al., 2021, 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, Vol: 3, Pages: 204-211, ISSN: 0894-2684

Background: Functional respiratory imaging (FRI) is a computational fluid dynamics-based technique using three-dimensional models of human lungs and formulation profiles to simulate aerosol deposition.Methods: FRI was used to evaluate lung deposition of extrafine beclomethasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) and extrafine BDP/FF delivered through pressurized metered dose inhalers and to compare results with reference gamma scintigraphy data. FRI combined high-resolution computed tomography scans of 20 patients with moderate-to-severe chronic obstructive pulmonary disease (mean forced expiratory volume in 1 second 42% predicted) with in silico computational flow simulations, and incorporated drug delivery parameters to calculate aerosol airway deposition. Inhalation was simulated using profiles obtained from real-life measurements.Results: Total lung deposition (proportion deposited in intrathoracic region) was similarly high for both products, with mean ± standard deviation (SD) values of 31.0% ± 5.7% and 28.1% ± 5.2% (relative to nominal dose) for BDP/FF/GB and BDP/FF, respectively. Pairwise comparison of the deposition of BDP and FF gave a mean intrathoracic BDP/FF/GB:BDP/FF deposition ratio of 1.10 (p = 0.0405). Mean intrathoracic, central and peripheral deposition ratios for BDP were 1.09 (95% confidence interval [CI]: 1.05–1.14), 0.92 (95% CI: 0.89–0.96), and 1.20 (95% CI: 1.15–1.26), respectively, and for FF were 1.11 (95% CI: 1.07–1.15), 0.94 (95% CI: 0.91–0.98), and 1.21 (95% CI: 1.15–1.27), within the bioequivalence range (0.80–1.25) for intrathoracic and central regions, and slightly exceeding the upper boundary in the peripheral region. Mean ± SD central:peripheral deposition (C:P) was 0.48 ± 0.13 for BDP/FF/GB and 0.62 ± 0.17 for BDP/F

Journal article

Kocks JWH, Andringa HJH, van Heijst E, Louis R, Ojanguren Arranz I, Riemersma RA, Ryan D, Usmani OS, Flokstra-de Blok BMJet al., 2021, Aeroallergen sensitization for detecting asthma in primary care: A diagnostic test accuracy study, CLINICAL AND EXPERIMENTAL ALLERGY, Vol: 51, Pages: 1080-1084, ISSN: 0954-7894

Journal article

Bousquet J, Jutel M, Akdis CA, Klimek L, Pfaar O, Nadeau KC, Eiwegger T, Bedbrook A, Ansotegui IJ, Anto JM, Bachert C, Bateman ED, Bennoor KS, Berghea EC, Bergmann K-C, Blain H, Bonini M, Bosnic-Anticevich S, Boulet L-P, Brussino L, Buhl R, Camargos P, Canonica GW, Cardona V, Casale T, Chinthrajah S, Akdis M, Chivato T, Christoff G, Cruz AA, Czarlewski W, Del Giacco S, Du H, El-Gamal Y, Fokkens WJ, Fonseca JA, Gao Y, Gaga M, Gemicioglu B, Gotua M, Haahtela T, Halpin D, Hamelmann E, Hoffmann-Sommergruber K, Humbert M, Ilina N, Ivancevich J-C, Joos G, Khaitov M, Kirenga B, Knol EF, Ko FW, Koskinen S, Kowalski ML, Kraxner H, Kudlay D, Kuna P, Kupczyk M, Kvedariene V, Abdul Latiff AH, Le LT, Levin M, Larenas-Linnemann D, Louis R, Masjedi MR, Melen E, Mihaltan F, Milenkovic B, Mohammad Y, Morais-Almeida M, Mullol J, Namazova L, Neffen H, Nunes E, O'Byrne P, O'Hehir R, O'Mahony L, Ohta K, Okamoto Y, Onorato GL, Panzner P, Papadopoulos NG, Passalacqua G, Patella V, Pawankar R, Pham-Thi N, Pigearias B, Popov TA, Puggioni F, Regateiro FS, Rolla G, Rottem M, Samolinski B, Sastre J, Schwarze J, Sheikh A, Scichilone N, Soto-Quiros M, Soto-Martinez M, Sova M, Nicola S, Stelmach R, Suppli-Ulrik C, Taborda-Barata L, To T, Tomazic P-V, Toppila-Salmi S, Tsiligianni I, Usmani O, Valiulis A, Ventura MT, Viegi G, Vontetsianos T, Wang DY, Williams S, Wong GWK, Yorgancioglu A, Zernotti M, Zidarn M, Zuberbier T, Agache Iet al., 2021, ARIA-EAACI statement on asthma and COVID-19 (June 2, 2020), Allergy, Vol: 76, Pages: 689-697, ISSN: 0105-4538

Journal article

Garner J, Biddiscombe MF, Meah S, Lewis A, Buttery SC, Hopkinson NS, Kemp SV, Usmani OS, Shah PL, Verbanck Set al., 2021, Endobronchial valve lung volume reduction and small airways function., American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 1576-1579, ISSN: 1073-449X

Journal article

Haughney J, Lee AJ, McKnight E, Pertsovskaya I, O'Driscoll M, Usmani OSet al., 2021, Peak inspiratory flow measured at different inhaler resistances in patients with asthma, Journal of Allergy and Clinical Immunology: In Practice, Vol: 9, Pages: 890-896, 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.

Journal article

Soni S, Garner J, O'Dea K, Kohn M, Finney L, Tirlapur N, Srikanthan K, aboelhassan A, Singh S, Wilson M, Wedzicha J, Kemp S, Usmani O, Shah P, Takata Met al., 2021, Intra-alveolar neutrophil-derived microvesicles are associated with disease severity in COPD, American Journal of Physiology: Lung Cellular and Molecular Physiology, Vol: 320, Pages: L73-L83, 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.

Journal article

Price D, Jones R, Pfister P, Cao H, Carter V, Kemppinen A, Holzhauer B, Kaplan A, Clark A, Halpin DM, Pinnock H, Chalmers JD, van Boven JFM, Beeh KM, Kostikas K, Roche N, Usmani O, Mastoridis Pet al., 2021, Maximizing Adherence and Gaining New Information For Your Chronic Obstructive Pulmonary Disease (MAGNIFY COPD): Study Protocol for the Pragmatic, Cluster Randomized Trial Evaluating the Impact of Dual Bronchodilator with Add-On Sensor and Electronic Monitoring on Clinical Outcomes, PRAGMATIC AND OBSERVATIONAL RESEARCH, Vol: 12, Pages: 25-35, ISSN: 1179-7266

Journal article

Dreher M, Price D, Gardev A, Peeters P, Arora S, van der Sar-van der Brugge S, Dekhuijzen R, Usmani OSet al., 2021, Patient perceptions of the re-usable Respimatt(R) Soft Mist (TM) inhaler in current users and those switching to the device: A real-world, non-interventional COPD study, Chronic Respiratory Disease, Vol: 18, Pages: 1-10, ISSN: 1479-9723

The Respimat® Soft Mist™ inhaler (SMI) has recently been improved, with a re-usable device replacing the disposable version. Certain countries are currently phasing out the disposable inhaler. This study aimed to assess patient satisfaction with and preference for the re-usable device. This 4–6-week, multicentre, open-label, prospective, real-world, non-interventional study was conducted across six European countries. Patients with chronic obstructive pulmonary disease were enrolled between October and December 2019, in three cohorts: (1) currently using the re-usable Respimat SMI; (2) switched from disposable Respimat SMI at study entry; and (3) naïve to any Respimat SMI. Patients were assessed using the Patient Satisfaction and Preference Questionnaire (PASAPQ) and Ease of Handling Questionnaire. In total, 262 patients were enrolled. At follow-up, the mean PASAPQ score was 83.3/100 overall, with similar results across all three patient cohorts. Most patients were ‘satisfied’ or ‘very satisfied’ with the re-usable device. The overall score for willingness to continue using the device was 87.8/100. In total, 13 adverse events were recorded, none of which was classified as serious. This study provides real-world evidence for practitioners to start patients on Respimat re-usable, irrespective of a patient’s prior experience with this inhaler.

Journal article

Almeshari MA, Alobadidi NY, Sapey E, Usmani O, Stockley RA, Stockley JAet al., 2021, Small Airways Response to Bronchodilators in Adults with Asthma or COPD: A Systematic Review, INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Vol: 16, Pages: 3065-3082, ISSN: 1178-2005

Journal article

Pleasants RA, Tilley SL, Hickey AJ, Usmani OSet al., 2021, User-life of ICS/LABA inhaler devices should be considered when prescribed as relievers, EUROPEAN RESPIRATORY JOURNAL, Vol: 57, ISSN: 0903-1936

Journal article

Bousquet J, Anto JM, Bachert C, Haahtela T, Zuberbier T, Czarlewski W, Bedbrook A, Bosnic-Anticevich S, Walter Canonica G, Cardona V, ElisioCosta, Cruz AA, Erhola M, Fokkens WJ, Fonseca JA, Illario M, CarlosIvancevich J, Jutel M, Klimek L, PiotrKuna, Kvedariene V, Le L, Larenas-Linnemann D, Laune D, Lourenço OM, Melén E, Mullol J, Niedoszytko M, Odemyr M, Okamoto Y, Papadopoulos NG, Patella V, Pfaar O, Pham-Thi N, Rolland C, Samolinski B, Sheikh A, Sofiev M, SuppliUlrik C, Todo-Bom A, Tomazic PV, Toppila-Salmi S, Tsiligianni I, Valiulis A, Valovirta E, Ventura M-T, Walker S, Williams S, Yorgancioglu A, Agache I, Akdis CA, Almeida R, Ansotegui IJ, Annesi-Maesano I, Arnavielhe S, Basagaña X, Bateman E, Bédard A, Bedolla-Barajas M, Becker S, Bennoor KS, Benveniste S, Bergmann KC, Bewick M, Bialek S, Billo N, Bindslev-Jensen C, Bjermer L, Blain H, Bonini M, Bonniaud P, Bosse I, Bouchard J, Boulet LP, Bourret R, Boussery K, Braido F, Briedis V, Briggs A, Brightling CE, JanBrozek, Brusselle G, Brussino L, Buhl R, Buonaiuto R, Calderon MA, Camargos P, Camuzat T, Caraballo L, Carriazo AM, Carr W, Cartier C, Casale T, Cecchi L, Cepeda Sarabia AM, Chavannes N, Chkhartishvili E, Chu DK, Cingi C, Correia de Sousa J, Costa DJ, Courbis AL, Custovic A, Cvetkosvki B, D'Amato G, da Silva J, Dantas C, Dokic D, Dauvilliers Y, De Feo G, De Vries G, Devillier P, Di Capua S, Dray G, Dubakiene R, Durham SR, Dykewicz M, Ebisawa M, Gaga M, El-Gamal Y, Heffler E, Emuzyte R, Farrell J, Fauquert J-L, Fiocchi A, Fink-Wagner A, Fontaine J-F, Fuentes Perez JM, Gemicioğlu B, Gamkrelidze A, Garcia-Aymerich J, Gevaert P, Gomez M, González Diaz S, Gotua M, Guldemond NA, Guzmán M-A, Hajjam J, Huerta Villalobos YR, Humbert M, Iaccarino G, Ierodiakonou D, TomohisaIinuma, Jassem E, Joos G, Jung K-S, Kaidashev I, Kalayci O, Kardas P, Keil T, Khaitov M, Khaltaev N, Kleine-Tebbe J, Kouznetsov R, Kowalski ML, Kritikos V, Kull I, La Grutta S, Leonardini L, Ljungberg H, Lieberman P, Lipworth B, Lodrup Carlet 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.

Journal article

Usmani OS, Roche N, Jenkins M, Stjepanovic N, Mack P, De Backer Wet 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

Journal article

Alzahabi KH, Usmani O, Georgiou TK, Ryan MP, Robertson BD, Tetley TD, Porter AEet 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

Tuberculosis (TB) is caused by a bacterial infection that affects a number of human organs, primarily the lungs, but also the liver, spleen, and spine, causing key symptoms of fever, fatigue, and persistent cough, and if not treated properly, can be fatal. Every year, 10 million individuals become ill with active TB resulting with a mortality approximating 1.5 million. Current treatment guidelines recommend oral administration of a combination of first-line anti-TB drugs for at least 6 months. While efficacious under optimum conditions, ‘Directly Observed Therapy Short-course’ (DOTS) is not without problems. The long treatment time and poor pharmacokinetics, alongside drug side effects lead to poor patient compliance and has accelerated the emergence of multi-drug resistant (MDR) organisms. All this, combined with the limited number of newly discovered TB drugs to treat MDR-TB and shorten standard therapy time, has highlighted the need for new targeted drug delivery systems. In this respect, there has been recent focus on micro- and nano-particle technologies to prepare organic or/and metal particles loaded with TB drugs to enhance their efficacy by targeted delivery via the inhaled route. In this review, we provide a brief overview of the current epidemiology of TB, and risk factors for progression of latent stage tuberculosis (LTBI) to the active TB. We identify current TB treatment regimens, newly discovered TB drugs, and identify studies that have used micro- or nano-particles technologies to design a reliable inhalation drug delivery system to treat TB more effectively.

Journal article

Soriano JB, Anzueto A, Anticevich SB, Kaplan A, Miravitlles M, Usmani O, Papadopoulos NG, Puggioni F, Canonica GW, Roche Net al., 2020, Face masks, respiratory patients and COVID-19, European Respiratory Journal, Vol: 56, ISSN: 0903-1936

Journal article

Usmani OS, Scichilone N, Mignot B, Belmans D, Van Holsbeke C, De Backer J, De Maria R, Cuoghi E, Topole E, Georges Get al., 2020, Airway deposition of extrafine inhaled triple therapy in patients with COPD: A model approach based on functional respiratory imaging computer simulations, The International Journal of Chronic Obstructive Pulmonary Disease, Vol: 15, Pages: 2433-2440, ISSN: 1176-9106

Introduction: There is a clear correlation between small airways dysfunction and poor clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), and it is therefore important that inhalation therapy (both bronchodilator and anti-inflammatory) can deposit in the small airways. Two single-inhaler triple therapy (SITT) combinations are currently approved for the maintenance treatment of COPD: extrafine formulation beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB), and non-extrafine formulation fluticasone furoate/vilanterol/umeclidinium (FluF/VI/UMEC). This study evaluated the lung deposition of the inhaled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs.Materials and Methods: Lung deposition was estimated in-silico using functional respiratory imaging, a validated technique that uses aerosol delivery performance profiles, patients’ high-resolution computed tomography (HRCT) lung scans, and patient-derived inhalation profiles to simulate aerosol lung deposition.Results: HRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV1) ranging from 19.3% to 66.0% predicted. For intrathoracic deposition (as a percentage of the emitted dose), deposition of the ICS component was higher from BDP/FF/GB than FluF/VI/UMEC; the two triple therapies had similar performance for both the LABA component and the LAMA component. Peripheral deposition of all three components was higher with BDP/FF/GB than FluF/VI/UMEC. Furthermore, the ratios of central to peripheral deposition for all three components of BDP/FF/GB were < 1, indicating greater peripheral than central deposition (0.48± 0.13, 0.48± 0.13 and 0.49± 0.13 for BDP, FF and GB, respectively; 1.96± 0.84, 0.97± 0.34 and 1.20± 0.48 for FluF, VI and UMEC, respecti

Journal article

Stanford G, Davies JC, Usmani O, Banya W, Charman S, Jones M, Simmonds NJ, Bilton Det 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.

Journal article

Bonini M, Cilluffo G, La Grutta S, Boccabella C, Usmani O, Viegi G, Palange Pet al., 2020, Anti-muscarinic drugs as preventive treatment of exercise-induced bronchoconstriction (EIB) in children and adults, RESPIRATORY MEDICINE, Vol: 172, ISSN: 0954-6111

Journal article

Baldi S, Usmani O, Van Holsbeke C, Mignot B, Panni I, Girardello L, De Backer J, Georges G, De Backer Wet 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

Conference paper

Kerkhof M, Chaudhry I, Pavord ID, Miravitlles M, Rhee CK, Halpin DMG, Usmani OS, Jones R, Kocks J, Alacqua M, Morris T, Kaplan A, Price DBet al., 2020, Blood eosinophil count predicts treatment failure and hospital readmission for COPD, ERJ OPEN RESEARCH, Vol: 6

Journal article

Israel S, Kumar A, DeAngelis K, Aurivillius M, Dorinsky P, Roche N, Usmani OSet 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.

Journal article

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