Publications
313 results found
Price DB, Bosnic-Anticevich S, Pavord ID, et al., 2019, Association of elevated fractional exhaled nitric oxide concentration and blood eosinophil count with severe asthma exacerbations, Clinical and Translational Allergy, Vol: 9, ISSN: 2045-7022
BackgroundBlood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO) concentration are established biomarkers in asthma, associated particularly with the risk of exacerbations. We evaluated the relationship of BEC and FeNO as complementary and independent biomarkers of severe asthma exacerbations.MethodsThis observational study included data from the Optimum Patient Care Research Database. Asthma patients (18–80 years) with valid continuous data for 1 year before FeNO reading, ≥ 1 inhaled corticosteroid prescription, and BEC recorded ≤ 5 years before FeNO reading were separated into cohorts. Categorisation 1 was based on the American Thoracic Society criteria for elevated FeNO concentration (high: ≥ 50 ppb; non-high: < 25 ppb) and BEC (high: ≥ 0.300 × 109 cells/L; non-high: < 0.300 × 109 cells/L). Categorisation 2 (FeNO concentration, high: ≥ 35 ppb; non-high: < 35 ppb) was based on prior research. Reference groups included patients with neither biomarker raised.ResultsIn categorisation 1, patients with either high FeNO or high BEC (n = 200) had a numerically greater exacerbation rate (unadjusted rate ratio, 1.31 [95% confidence interval: 0.97, 1.76]) compared with patients in the reference group. Combination of high FeNO and high BEC (n = 27) resulted in a significantly greater exacerbation rate (3.67 [1.49, 9.04]). Similarly, for categorisation 2, when both biomarkers were raised (n = 53), a significantly greater exacerbation rate was observed (1.72 [1.00, 2.93]).ConclusionThe combination of high FeNO and high BEC was associated with significantly increased severe exacerbation rates in the year preceding FeNO reading, suggesting that combining FeNO and BEC measurements in primary care may identify asthma patients at risk of exacerb
Bousquet J, Nhan P-T, Bedbrook A, et al., 2019, Next-generation care pathways for allergic rhinitis and asthma multimorbidity: a model for multimorbid non-communicable diseases, JOURNAL OF THORACIC DISEASE, Vol: 11, Pages: 3633-3641, ISSN: 2072-1439
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- Citations: 8
Usmani O, 2019, ROLE OF SMART INHALER TECHNOLOGY IN ASTHMA - ADHERENCE AND BEYOND, Publisher: MARY ANN LIEBERT, INC, Pages: A5-A6, ISSN: 1941-2711
Sovershaeva E, Kranzer K, Mchugh G, et al., 2019, History of tuberculosis is associated with lower exhaled nitric oxide levels in HIV-infected children, AIDS, Vol: 33, Pages: 1711-1718, ISSN: 0269-9370
OBJECTIVE: HIV disrupts host defense mechanisms and maintains chronic inflammation in the lung. Nitric oxide (NO) is a marker of lung inflammation and can be measured in the exhaled air. We investigated the relationship between exhaled NO (eNO), HIV status and airway abnormalities in perinatally HIV-infected children aged 6 to 19 years. DESIGN: Cross-sectional study. METHODS: HIV-infected individuals on antiretroviral therapy and HIV-uninfected children with no active tuberculosis (TB) or acute respiratory tract infection were recruited from a public hospital in Harare, Zimbabwe. Clinical history was collected and eNO testing and spirometry was performed. The association between eNO and explanatory variables (HIV, FEV1 z-score, CD4 count, viral load, history of TB) was investigated using linear regression analysis adjusted for age, sex and time of eNO testing. RESULTS: In total 222 HIV-infected and 97 HIV-uninfected participants were included. Among HIV-infected participants 57 (25.7%) had a history of past TB; 56 (25.2%) had airway obstruction, but no prior TB. HIV status was associated with lower eNO level (mean ratio 0.79 (95% CI 0.65-0.97), p = 0.03). Within the HIV-infected group, history of past TB was associated with lower eNO levels after controlling for age, sex and time of eNO testing (0.79 (95% CI 0.67-0.94), p = 0.007). CONCLUSION: HIV infection and history of TB were associated with lower eNO levels. eNO levels may be a marker of HIV- and TB-induced alteration in pulmonary physiology; further studies focused on potential causes for lower eNO levels in HIV and TB are warranted.
Postma DS, Brightling C, Baldi S, et al., 2019, Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study., Lancet Respir Med, Vol: 7, Pages: 402-416
BACKGROUND: Small airways dysfunction (SAD) is well recognised in asthma, yet its role in the severity and control of asthma is unclear. This study aimed to assess which combination of biomarkers, physiological tests, and imaging markers best measure the presence and extent of SAD in patients with asthma. METHODS: In this baseline assessment of a multinational prospective cohort study (the Assessment of Small Airways Involvement in Asthma [ATLANTIS] study), we recruited participants with and without asthma (defined as Global Initiative for Asthma severity stages 1-5) from general practices, the databases of chest physicians, and advertisements at 29 centres across nine countries (Brazil, China, Germany, Italy, Spain, the Netherlands, the UK, the USA, and Canada). All participants were aged 18-65 years, and participants with asthma had received a clinical diagnosis of asthma more than 6 months ago that had been confirmed by a chest physician. This diagnosis required support by objective evidence at baseline or during the past 5 years, which could be: positive airway hyperresponsiveness to methacholine, positive reversibility (a change in FEV1 ≥12% and ≥200 mL within 30 min) after treatment with 400 μg of salbutamol in a metered-dose inhaler with or without a spacer, variability in peak expiratory flow of more than 20% (measured over 7 days), or documented reversibility after a cycle (eg, 4 weeks) of maintenance anti-asthma treatment. The inclusion criteria also required that patients had stable asthma on any previous regular asthma treatment (including so-called rescue β2-agonists alone) at a stable dose for more than 8 weeks before baseline and had smoked for a maximum of 10 pack-years in their lifetime. Control group participants were recruited by advertisements; these participants were aged 18-65 years, had no respiratory symptoms compatible with asthma or chronic obstructive pulmonary disease, normal spirometry, and normal airways responsiveness, an
Usmani OS, 2019, Choosing the right inhaler for your asthma or COPD patient, Therapeutics and Clinical Risk Management, Vol: 15, Pages: 461-472, ISSN: 1176-6336
Appropriate selection and correct use of inhalation devices is an integral component in the management of asthma and chronic obstructive pulmonary disease (COPD). It is well known that there are many challenges with the use of inhalers, and no one device suits all patients. Challenges can range from difficulties related to lung disease severity and pulmonary function to physical considerations, including manual dexterity and comorbidities such as arthritis. In terms of device selection and adherence, patient engagement and satisfaction are also important factors to consider. Furthermore, problems with inhaler use can be most evident in children and older patients. Here, we discuss aspects for consideration with commonly used devices, including nebulizers, pressurized metered-dose inhalers, dry powder inhalers, and the soft mist inhaler. As each inhaler offers varying technical properties, a tailored and personalized approach to the selection of the most appropriate device for the patient is highly recommended in order to increase the likelihood of achieving improved disease outcomes and enhance persistence with device adherence. Importantly, education and support is crucial, not only to enable patients to recognize the need for optimal disease management, but also to help them develop good inhaler technique. In addition, health care professionals should also aim to increase their knowledge of the devices they prescribe, and develop systems to ensure that they offer comprehensive support to patients in clinical practice. Considering these aspects, this review discusses potential strategies to help address the challenges of inhaler use in asthma and COPD.
Hakim A, Khan Y, Esteban I, et al., 2019, Low-dose budesonide/formoterol counteracts airway inflammation and improves lung function in COPD, American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 662-664, ISSN: 1073-449X
The latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) document recommends new treatment algorithms, with inhaled corticosteroids (ICS) use only in moderate-to-severely symptomatic COPD patients with repeated exacerbations, where the emphasis is to review ICS use and to reduce ICS dosing (1). Indeed, safety concerns of pneumonia (2) with high-dose ICS has further concerted focus upon using appropriate doses of ICS. It is well-established that ICS in combination with long-acting β2-adrenoceptor agonist (LABA) can decrease exacerbations, improve symptomsand increase quality of life in patients with COPD (3-4), but nonetheless, the rationale to consider step-down of ICS is supported by several clinical studies (5). The Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial studied severe COPD patients on therapy with ICS, LAMA and LABA, where stepwise withdrawal of ICS did not lead to an increase in exacerbations compared to continued ICS use (6). Determining the optimal dose of ICS and LABA combination therapy is of great biological and clinical importance in order to address safety concerns associated with high-dose ICS use. There is in vitro evidence to support the clinical practice of using low-dose ICS. Low-dose ICS in combination with LABA enhances corticosteroid function by enhancing glucocorticoid receptor (GR) activity (7) and suppresses the release of inflammatory mediators (8). However, it is unknown whether this observation of enhanced corticosteroid function with low-dose ICS/LABA has a direct effect on airways inflammation and lung function. Our study investigated the cellular function that may be relevant and underpin the clinical approach to lowering the dose of ICS therapy in COPD patients. We compared the single administra
Schleich F, Bikov A, Mathioudakis AG, et al., 2019, Research highlights from the 2018 European Respiratory Society International Congress: airway disease., ERJ Open Research, Vol: 5, ISSN: 2312-0541
The annual European Respiratory Society (ERS) International Congress (held in Paris in 2018) was once again a platform for discussion of the highest-quality scientific research, cutting-edge techniques and innovative new therapies within the respiratory field. This article discusses only some of the high-quality research studies presented at this year's Congress, with a particular focus on airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and cough, as presented through Assembly 5 of the ERS (Airway Diseases: Asthma and COPD). The authors establish the key take-home messages of these studies, compare their findings and place them in the context of current understanding.
Usmani O, Roche N, Marshall J, et al., 2019, An innovative corticosteroid/long-acting beta(2)-agonist breath-triggered inhaler: facilitating lung delivery of fluticasone propionate/formoterol fumarate for the treatment of asthma, EXPERT OPINION ON DRUG DELIVERY, Vol: 16, Pages: 1367-1380, ISSN: 1742-5247
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- Citations: 6
Usmani OS, Scullion J, Keeley D, 2019, Our planet or our patients-is the sky the limit for inhaler choice?, Lancet Respiratory Medicine, Vol: 7, Pages: 11-13, ISSN: 2213-2600
Kerkhof M, Chaudhry I, Kocks J, et al., 2019, Eosinophil Counts as a Biomarker of Oral Corticosteroid Treatment Success for Patients with COPD, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Dhand R, Hickey A, Guranlioglu D, et al., 2019, Does Inhaler Continuity and Familiarity Provide Clinical Benefits for Management of Patients with Chronic Obstructive Pulmonary Disease or Asthma?, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Lavorini F, Buttini F, Usmani OS, 2019, 100 Years of Drug Delivery to the Lungs, CONCEPTS AND PRINCIPLES OF PHARMACOLOGY, Vol: 260, Pages: 143-159, ISSN: 0171-2004
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- Citations: 22
Kerkhof M, Chaudhry I, Kocks J, et al., 2019, Disease Severity of Patients with High Blood Eosinophil Counts Treated for COPD Exacerbation with or Without Oral Corticosteroids, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Garcia-Marcos L, Edwards J, Kennington E, et al., 2018, Priorities for future research into asthma diagnostic tools: A PAN-EU consensus exercise from the European asthma research innovation partnership (EARIP), Clinical and Experimental Allergy, Vol: 48, Pages: 104-120, ISSN: 0954-7894
The diagnosis of asthma is currently based on clinical history, physical examination and lung function, and to date, there are no accurate objective tests either to confirm the diagnosis or to discriminate between different types of asthma. This consensus exercise reviews the state of the art in asthma diagnosis to identify opportunities for future investment based on the likelihood of their successful development, potential for widespread adoption and their perceived impact on asthma patients. Using a two-stage e-Delphi process and a summarizing workshop, a group of European asthma experts including health professionals, researchers, people with asthma and industry representatives ranked the potential impact of research investment in each technique or tool for asthma diagnosis and monitoring. After a systematic review of the literature, 21 statements were extracted and were subject of the two-stage Delphi process. Eleven statements were scored 3 or more and were further discussed and ranked in a face-to-face workshop. The three most important diagnostic/predictive tools ranked were as follows: “New biological markers of asthma (eg genomics, proteomics and metabolomics) as a tool for diagnosis and/or monitoring,” “Prediction of future asthma in preschool children with reasonable accuracy” and “Tools to measure volatile organic compounds (VOCs) in exhaled breath.”.
Grigg J, Nibber A, Paton JY, et al., 2018, Matched cohort study of therapeutic strategies to prevent preschool wheezing/asthma attacks, Journal of Asthma and Allergy, Vol: 11, ISSN: 1178-6965
Background: An inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA) may prevent wheezing/asthma attacks in preschoolers with recurrent wheeze when added to short-acting β-agonist (SABA).Objective: The aim of this historical matched cohort study was to assess the effectiveness of these treatments for preventing wheezing/asthma attacks.Methods: Electronic medical records from the Optimum Patient Care Research Database were used to characterize a UK preschool population (1–5 years old) with two or more episodes of wheezing during 1 baseline year before first prescription (index date) of ICS or LTRA, or repeat prescription of SABA. Children initiating ICS or LTRA on the index date were matched 1:4 to those prescribed only SABA for age, sex, year of index prescription, mean baseline SABA dose, baseline attacks, baseline antibiotic prescriptions, and eczema diagnosis. Wheezing/asthma attacks (defined as asthma-related emergency attendance, hospital admission, or acute oral corticosteroid prescription) during 1 outcome year were compared using conditional logistic regression.Results: Matched ICS and SABA cohorts included 990 and 3,960 children, respectively (61% male; mean [SD] age 3.2 [1.3] years), and matched LTRA and SABA cohorts included 259 and 1,036 children, respectively (65% male; mean [SD] age 2.6 [1.2] years). We observed no significant difference between matched cohorts in the odds of a wheezing/asthma attack: ICS vs SABA, OR (95% CI) 1.01 (0.85–1.19) and LTRA vs SABA, OR (95% CI) 1.28 (0.96–1.72).Conclusion: We found no evidence that initiation of ICS or LTRA therapy is associated with fewer attacks during 1 outcome year than SABA alone for a heterogeneous group of preschool children with recurrent wheeze in the real-life clinical setting.
Moroni-Zentgraf P, Usmani OS, Halpin DMG, 2018, Inhalation devices, Canadian Respiratory Journal, Vol: 2018, ISSN: 1198-2241
Biddiscombe M, Saleem A, Meah S, et al., 2018, Efficacy of the device in targeting tiotropium to the small airways in COPD, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 3
Ghazwani A, Biddiscombe M, Usmani O, 2018, Comparing Lung Geometrical Areas of interest in Gamma Scintigraphy as Assessment Tool for Inhaled Drug Deposition, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Garner J, Soni S, O'Dea K, et al., 2018, Late Breaking Abstract - Intra-alveolar neutrophil-derived microvesicles: a biomarker of COPD severity, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Bonini M, Messina J, Petrarulo S, et al., 2018, T2-endotype predicts bronchodilator (BD) response in Exercise-Induced Bronchoconstriction (EIB), 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 1
Bonini M, Messina J, Petrarulo S, et al., 2018, Baseline FeNO is an independent predictive marker of Exercise-Induced Bronchoconstriction (EIB), 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 2
Usmani O, Vos W, Mignot B, et al., 2018, Lung deposition of extrafine inhaled corticosteroid (ICS)-containing fixed combinations drug in COPD patients using Functional Respiratory Imaging (FRI)., 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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- Citations: 5
Saleem A, Attar-Zadeh D, Khambh J, et al., 2018, Standardising inhaler technique videos in a clinician and patient app, 28th International Congress of the European-Respiratory-Society (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Biddiscombe MF, Usmani OS, 2018, Is there room for further innovation in inhaled therapy for airways disease?, Breathe, Vol: 14, Pages: 216-223, ISSN: 2073-4735
Inhaled medication is the cornerstone in the treatment of patients across a spectrum of respiratory diseases including asthma and chronic obstructive pulmonary disease. The benefits of inhaled therapy have long been recognised but the most important innovations have occurred over the past 60 years, beginning with the invention of the pressurised metered dose inhaler. However, despite over 230 different device and drug combinations currently being available, disease control is far from perfect.Here we look at how innovation in inhaler design may improve treatments for respiratory diseases and how new formulations may lead to treatments for diseases beyond the lungs. We look at the three main areas where innovation in inhaled therapy is most likely to occur: 1) device engineering and design; 2) chemistry and formulations; and 3) digital technology associated with inhalers. Inhaler design has improved significantly but considerable challenges still remain in order to continually innovate and improve targeted drug delivery to the lungs. Healthcare professionals want see innovations that motivate their patients to achieve their goal of improving their health, through better adherence to treatment. Patients want devices that are easy to use and to see that their efforts are rewarded by improvements in their condition.Key points The dictionary definition of innovation is the introduction of new things, ideas or ways of doing something. We show how this definition can be applied to inhaled therapy. We take a look at the past to see what drove innovation in inhaler design and how this has led to the current devices. We look at the current drivers of innovation in engineering, chemistry and digital technology and predict how this may translate to new devices. Can innovation help the healthcare professional manage their patients better? What does the patient expect from innovation in their device?Educational aims To understand the importance of inhaled me
Satia I, Badri H, Lahousse L, et al., 2018, Airways diseases: asthma, COPD and chronic cough highlights from the European Respiratory Society Annual Congress 2018, JOURNAL OF THORACIC DISEASE, Vol: 10, Pages: S2992-S2997, ISSN: 2072-1439
Maneechotesuwan K, Yao X, Ito K, et al., 2018, Correction: Suppression of GATA-3 nuclear import and phosphorylation: a novel mechanism of corticosteroid action in allergic disease, PLoS Medicine, Vol: 15, ISSN: 1549-1277
[This corrects the article DOI: 10.1371/journal.pmed.1000076.].
Vincken W, Levy ML, Scullion J, et al., 2018, Spacer devices for inhaled therapy: why use them, and how?, ERJ Open Research, Vol: 4, ISSN: 2312-0541
We present an extensive review of the literature to date pertaining to the rationale for using a spacer/valved holding chamber (VHC) to deliver inhaled therapy from a pressurised, metered-dose inhaler, a discussion of how the properties of individual devices may vary according to their physical characteristics and materials of manufacture, the potential risks and benefits of ancillaries such as valves, and the evidence that they contribute tangibly to the delivery of therapy. We also reiterate practical recommendations for the correct usage and maintenance of spacers/VHCs, which we trust offer practical help and advice to patients and healthcare professionals alike.
van Geffen WH, Hajian B, Vos W, et al., 2018, Functional respiratory imaging: heterogeneity of acute exacerbations of COPD, International Journal of Chronic Obstructive Pulmonary Disease, Vol: 13, Pages: 1783-1792, ISSN: 1176-9106
Background: Exacerbations of COPD are a major burden to patients, and yet little is understood about heterogeneity. It contributes to the current persistent one-size-fits-all treatment. To replace this treatment by more personalized, precision medicine, new insights are required. We assessed the heterogeneity of exacerbations by functional respiratory imaging (FRI) in 3-dimensional models of airways and lungs. Methods: The trial was designed as a multicenter trial of patients with an acute exacerbation of COPD who were assessed by FRI, pulmonary function tests, and patient-reported outcomes, both in the acute stage and during resolution. Results: Forty seven patients were assessed. FRI analyses showed significant improvements in hyperinflation (a decrease in total volume at functional residual capacity of -0.25±0.61 L, p≤0.01), airway volume at total lung capacity (+1.70±4.65 L, p=0.02), and airway resistance. As expected, these improvements correlated partially with changes in the quality of life and in conventional lung function test parameters. Patients with the same changes in pulmonary function differ in regional disease activity measured by FRI. Conclusion: FRI is a useful tool to get a better insight into exacerbations of COPD, and significant improvements in its indices can be demonstrated from the acute phase to resolution even in relatively small groups. It clearly visualizes the marked variability within and between individuals in ventilation and resistance during exacerbations and is a tool for the assessment of the heterogeneity of COPD exacerbations.
Sonnappa S, McQueen B, Postma DS, et al., 2018, Extrafine versus fine inhaled corticosteroids in relation to asthma control: a systematic review and meta-analysis of observational real-life studies, The journal of allergy and clinical immunology. In practice, Vol: 6, Pages: 907-915.e7, ISSN: 2213-2198
BACKGROUND: The particle size of inhaled corticosteroids (ICSs) may affect airway drug deposition and effectiveness. OBJECTIVE: To compare the effectiveness of extrafine ICSs (mass median aerodynamic diameter, <2 μm) versus fine-particle ICSs administered as ICS monotherapy or ICS-long-acting β-agonist combination therapy by conducting a meta-analysis of observational real-life asthma studies to estimate the treatment effect of extrafine ICSs. METHODS: MEDLINE and EMBASE databases were reviewed for asthma observational comparative effectiveness studies from January 2004 to June 2016. Studies were included if they reported odds and relative risk ratios and met all inclusion criteria (Respiratory Effectiveness Group/European Academy of Allergy and Clinical Immunology quality standards, comparison of extrafine ICSs with same or different ICS molecule, ≥12-month follow-up). End-point data (asthma control, exacerbations, prescribed ICS dose) were pooled. Random-effects meta-analysis modeling was used. The study protocol is published in the PROSPERO register CRD42016039137. RESULTS: Seven studies with 33,453 subjects aged 5 to 80 years met eligibility criteria for inclusion. Six studies used extrafine beclometasone propionate and 1 study used both extrafine beclometasone propionate and extrafine ciclesonide as comparators with fine-particle ICSs. The overall odds of achieving asthma control were significantly higher for extrafine ICSs compared with fine-particle ICSs (odds ratio, 1.34; 95% CI, 1.22-1.46). Overall exacerbation rate ratios (0.84; 95% CI, 0.73-0.97) and ICS dose (weighted mean difference, -170 μg; 95% CI, -222 to -118 μg) were significantly lower for extrafine ICSs compared with fine-particle ICSs. CONCLUSIONS: This meta-analysis demonstrates that extrafine ICSs have significantly higher odds of achieving asthma control with lower exacerbation rates at significantly lower prescribed doses than fine-particle ICSs.
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