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Refractory asthma

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https://www.readbyqxmd.com/read/28919788/innovative-treatments-for-severe-refractory-asthma-how-to-choose-the-right-option-for-the-right-patient
#1
REVIEW
Francesco Menzella, Carla Galeone, Francesca Bertolini, Claudia Castagnetti, Nicola Facciolongo
The increasing understanding of the molecular biology and the etiopathogenetic mechanisms of asthma helps in identification of numerous phenotypes and endotypes, particularly for severe refractory asthma. For a decade, the only available biologic therapy that met the unmet needs of a specific group of patients with severe uncontrolled allergic asthma has been omalizumab. Recently, new biologic therapies with different mechanisms of action and targets have been approved for marketing, such as mepolizumab. Other promising drugs will be available in the coming years, such as reslizumab, benralizumab, dupilumab and lebrikizumab...
2017: Journal of Asthma and Allergy
https://www.readbyqxmd.com/read/28918658/the-role-of-upper-airway-pathology-as-a-co-morbidity-in-severe-asthma
#2
Amelia Licari, Ilaria Brambilla, Maria De Filippo, Dimitri Poddighe, Riccardo Castagnoli, Gian Luigi Marseglia
Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple co-morbidities and risk factors. Several co-morbidities may contribute to worsen asthma control and complicate diagnostic and therapeutic management of severe asthmatic patients. Areas covered: A prevalent cluster of chronic upper airway co-morbid diseases is recognized in severe asthma. Evaluation for these disorders should always be considered in clinical practice. The aim of this review is to provide an updated overview of the prevalence, the pathogenetic mechanisms, the clinical impact and the therapeutic options for upper airway pathology in severe asthma, focusing on chronic rhinosinusitis and allergic rhinitis...
September 16, 2017: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/28910970/antibody-therapy-for-the-management-of-severe-asthma-with-eosinophilic-inflammation
#3
Ken Ohta, Hiroyuki Nagase, Maho Suzukawa, Shin Ohta
One of the characteristic features of asthma is chronic airway inflammation typically with eosinophil infiltration. Most asthmatics can be treated successfully with conventional treatment appropriate for their severity, but in some severe cases, asthma cannot be well controlled even with thorough treatment and this condition is known as 'refractory asthma'. To overcome severe refractory asthma, a new therapeutic strategy with biologics has been developed based on the knowledge of molecular mechanisms of airway inflammation in asthma, induced by the condition of high Th2-type responses and activation of eosinophils as well as allergic reactions...
July 1, 2017: International Immunology
https://www.readbyqxmd.com/read/28905471/novel-assessment-tool-to-detect-breathing-pattern-disorder-in-patients-with-refractory-asthma
#4
Sarah Todd, Emil S Walsted, Lizzie Grillo, Rebecca Livingston, Andrew Menzies-Gow, James H Hull
BACKGROUND AND OBJECTIVE: Breathing pattern disorder (BPD) can co-exist with and mimic asthma, acting to amplify symptoms and confound assessment of disease control, resulting in inappropriate treatment escalation. The aim of this research was to report the utility of a novel breathing pattern assessment tool (BPAT) to detect BPD in treatment-refractory asthma. METHODS: As a component of a multidisciplinary assessment, adult patients referred with treatment-refractory asthma underwent respiratory physiotherapy assessment to diagnose BPD...
September 14, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28865412/association-between-4259-t-g-and-574-g-t-polymorphisms-of-tim-3-with-asthma-in-an-iranian-population
#5
Maryam Sadri, Mazdak Ganjalikhani-Hakemi, Peyman Akbari, Rasoul Salehi, Sedighe Rastaghi, Ramin Ghasemi, Rezvan Meshkat
T-cell immunoglobulin and mucin domain (TIM)-3 have been shown to negatively regulate Th1 cell-mediated immunity. Activation of TIM-3 by galectin-9 induces Th1 cell apoptosis, which may contribute to skewing of immune response towards Th2-dominant immunity. The aim of this study was to determine whether certain genetic variations of TIM-3 influence predisposition to asthma in a sample of Iranian population. This case-control study was conducted on 209 patients with asthma and 200 healthy controls. The +4259 T>G and -574 G>T polymorphisms were detected using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and amplification refractory mutation system-PCR(ARMS-PCR)...
August 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28840844/increased-serum-il-17a-and-th2-cytokine-levels-in-patients-with-severe-uncontrolled-asthma
#6
Takehiro Hasegawa, Hitoshi Uga, Akio Mori, Hirokazu Kurata
Asthma is a syndrome of chronic bronchial inflammation and airway remodelling. Initially, asthma has been categorized into atopic and nonatopic types, based on antigen-specific IgE levels. Moreover, recently, asthma has been classified into different endotypes based on its pathophysiology, leading to the selection of the most optimal and effective therapies. Although T helper cell type 2 (Th2) cytokines were proven to play critical roles in atopic asthma, IL-17A has been reported to be involved in severe refractory asthma...
March 1, 2017: European Cytokine Network
https://www.readbyqxmd.com/read/28803775/pulmonary-function-in-patients-with-eosinophilic-chronic-rhinosinusitis
#7
Kensuke Uraguchi, Shin Kariya, Seiichiro Makihara, Mitsuhiro Okano, Takenori Haruna, Aiko Oka, Rumi Fujiwara, Yohei Noda, Kazunori Nishizaki
OBJECTIVE: There is a close relationship between upper and lower respiratory tract diseases. Chronic rhinosinusitis patients frequently have lung diseases including asthma and chronic obstructive pulmonary disease. Eosinophilic chronic rhinosinusitis is considered a refractory and intractable subtype of chronic rhinosinusitis. However, there has been no report on pulmonary function in patients with eosinophilic chronic rhinosinusitis. The purpose of this study is to examine the pulmonary function in eosinophilic chronic rhinosinusitis patients and non-eosinophilic chronic rhinosinusitis patients, and evaluate clinical factors associated with the pulmonary function of these patients...
August 10, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28783702/natural-killer-cell-mediated-inflammation-resolution-is-disabled-in-severe-asthma
#8
Melody G Duvall, Cindy Barnig, Manuela Cernadas, Isabell Ricklefs, Nandini Krishnamoorthy, Nicole L Grossman, Nirav R Bhakta, John V Fahy, Eugene R Bleecker, Mario Castro, Serpil C Erzurum, Benjamin M Gaston, Nizar N Jarjour, David T Mauger, Sally E Wenzel, Suzy A Comhair, Andrea M Coverstone, Merritt L Fajt, Annette T Hastie, Mats W Johansson, Michael C Peters, Brenda R Phillips, Elliot Israel, Bruce D Levy
Severe asthma is typically characterized by chronic airway inflammation that is refractory to corticosteroids and associated with excess morbidity. Patients were recruited into the National Heart, Lung, and Blood Institute-sponsored Severe Asthma Research Program and comprehensively phenotyped by bronchoscopy. Bronchoalveolar lavage (BAL) cells were analyzed by flow cytometry. Compared with healthy individuals (n = 21), patients with asthma (n = 53) had fewer BAL natural killer (NK) cells. Patients with severe asthma (n = 29) had a marked increase in the ratios of CD4(+) T cells to NK cells and neutrophils to NK cells...
March 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28762062/sequential-rituximab-and-omalizumab-for-the-treatment-of-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss-syndrome
#9
REVIEW
David Aguirre-Valencia, Iván Posso-Osorio, Juan-Carlos Bravo, Fabio Bonilla-Abadía, Gabriel J Tobón, Carlos A Cañas
Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms...
July 31, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28751262/do-individuals-with-asthma-experience-airway-hyper-responsiveness-after-exposure-to-nitrogen-dioxide
#10
Julie E Goodman, Erin M Kennedy, Mara Seeley
The current 100 ppb short-term National Ambient Air Quality Standard for NO2, and EPA's determination of a causal association for respiratory effects, are based in part on controlled human exposure studies evaluating airway hyper-responsiveness (AHR). A meta-analysis by Goodman et al. (2009) found increased AHR at 100 ppb NO2 but no clear concentration-response relationship up to 600 ppb, and an overall lack of an AHR effect for studies involving exercise or exposure to allergens. Several factors have been suggested to explain why effects on AHR are observed while people are at rest, but not during exercise or after exposure to allergens...
July 25, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28717087/pulmonary-intravascular-large-b-cell-lymphoma-ivlbcl-disguised-as-an-asthma-exacerbation-in-a-patient-with-asthma
#11
Tomohito Takeshige, Norihiro Harada, Yasuhito Sekimoto, Ryota Kanemaru, Takeo Tsutsumi, Kei Matsuno, Satomi Shiota, Azuchi Masuda, Akihiko Gotoh, Miki Asahina, Toshimasa Uekusa, Kazuhisa Takahashi
A 62-year-old man with asthma presented with a 1-month history of wheezing and exertional dyspnea. Although the wheezing symptoms disappeared after systemic corticosteroid therapy, the exertional dyspnea and hypoxemia did not improve. A diagnosis of intravascular large B-cell lymphoma (IVLBCL) with pulmonary involvement was suspected because of the increased serum lactic dehydrogenase (LDH) and soluble interleukin-2 receptor (sIL-2R) level, increased alveolar-arterial oxygen difference (AaDO2), decreased pulmonary diffusing capacity for carbon monoxide (DLCO) and scintigraphic, computed tomography (CT) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT findings...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28709761/central-nervous-system-involvement-in-eosinophilic-granulomatosis-with-polyangiitis-churg-strauss-report-of-26-patients-and-review-of-the-literature
#12
REVIEW
Raphaël André, Vincent Cottin, Jean-Luc Saraux, Gilles Blaison, Boris Bienvenu, Pascal Cathebras, Robin Dhote, Aurélie Foucher, Helder Gil, Joëlle Lapoirie, David Launay, Valentine Loustau, François Maurier, Edouard Pertuiset, Thierry Zénone, Jörg Seebach, Nathalie Costedoat-Chalumeau, Xavier Puéchal, Luc Mouthon, Loïc Guillevin, Benjamin Terrier
BACKGROUND: Although peripheral nervous system involvement is common in eosinophilic granulomatosis with polyangiitis (EGPA), central nervous system (CNS) manifestations are poorly described. This study aimed to describe CNS involvement in EGPA. PATIENTS AND METHODS: This retrospective, observational, multicenter study included patients with EGPA and CNS involvement affecting cranial nerves, brain and/or spinal cord. We also undertook a systematic literature review...
July 12, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28668237/point-of-care-blood-eosinophil-count-in-a-severe-asthma-clinic-setting
#13
Enrico Heffler, Giovanni Terranova, Carlo Chessari, Valentina Frazzetto, Claudia Crimi, Silvia Fichera, Giuseppe Picardi, Giuliana Nicolosi, Morena Porto, Rossella Intravaia, Nunzio Crimi
BACKGROUND: One of the main severe asthma phenotypes is severe eosinophilic or eosinophilic refractory asthma for which novel biologic agents are emerging as therapeutic options. In this context, blood eosinophil counts are one of the most reliable biomarkers. OBJECTIVE: To evaluate the performance of a point-of-care peripheral blood counter in a patients with severe asthma. METHODS: The blood eosinophil counts of 76 patients with severe asthma were evaluated by point-of-care and standard analyzers...
July 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28658551/spectrum-of-t-lymphocyte-activities-regulating-allergic-lung-inflammation
#14
REVIEW
Erwin W Gelfand, Anthony Joetham, Meiqin Wang, Katsuyuki Takeda, Michaela Schedel
Despite advances in the treatment of asthma, optimization of symptom control remains an unmet need in many patients. These patients, labeled severe asthma, are responsible for a substantial fraction of the disease burden. In these patients, research is needed to define the cellular and molecular pathways contributing to disease which in large part are refractory to corticosteroid treatment. The causes of steroid-resistant asthma are multifactorial and result from complex interactions of genetics, environmental factors, and innate and adaptive immunity...
July 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28638418/the-expression-of-stat3-and-stat5a-genes-in-severe-refractory-asthma
#15
Kayvan Saeedfar, Mehrdad Behmanesh, Esmaeil Mortaz, Mohammad Reza Masjedi
BACKGROUND: Despite being a high burden disorder, the pathogenesis of severe refractory asthma (SRA) is poorly understood. There are some evidences for the involvement of members of the signal transducer and activator of transcription (STAT) family, including STAT3 and STAT5a. Our study aimed to evaluate the gene expression of STAT3 and STAT5a in asthma and SRA to establish if there is an association. MATERIALS AND METHODS: Using quantitative real-time polymerase chain reactions (qRT-PCR), the transcript levels of STAT3 and STAT5a were evaluated in peripheral blood mononuclear lymphocytes (PBML) isolated from 13 patients with SRA, 14 with mild asthma, and 30 healthy volunteers...
2017: Tanaffos
https://www.readbyqxmd.com/read/28619778/in-patients-with-severe-uncontrolled-asthma-does-knowledge-of-adherence-and-inhaler-technique-using-electronic-monitoring-improve-clinical-decision-making-a-protocol-for-a-randomised-controlled-trial
#16
Matshediso C Mokoka, Lorna Lombard, Elaine M MacHale, Joanne Walsh, Breda Cushen, Imran Sulaiman, Damien Mc Carthy, Fiona Boland, Frank Doyle, Eoin Hunt, Desmond M Murphy, John Faul, Marcus Butler, Kathy Hetherington, J Mark FitzGerald, Job Fm van Boven, Liam G Heaney, Richard B Reilly, Richard W Costello
INTRODUCTION: Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes...
June 15, 2017: BMJ Open
https://www.readbyqxmd.com/read/28616286/severe-and-uncontrolled-asthma-in-china-a-cross-sectional-survey-from-the-australasian-severe-asthma-network
#17
Gang Wang, Fang Wang, Peter G Gibson, Michael Guo, Wei-Jie Zhang, Peng Gao, Hong-Ping Zhang, Erin S Harvey, Hui Li, Jie Zhang
BACKGROUND: Severe asthma is largely unexplored in the Chinese population. Patients with asthma underwent systematic evaluation, by investigating the characteristics of uncontrolled asthma and of asthma treated with three different controller therapies. METHODS: This multi-centre, real-world study was conducted from March 2014 to September 2015. Adults with stable asthma underwent assessment of medication use, asthma control, quality of life, psychological symptoms, work productivity and activity impairment, bronchodilator response and sputum induction...
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28588827/a-case-of-a-pulmonary-artery-sling-misdiagnosed-as-refractory-asthma-for-20%C3%A2-years
#18
Toshihide Inui, Hideyasu Yamada, Norihito Hida, Hideo Terashima, Takefumi Saito, Nobuyuki Hizawa
We report the case of a 25-year-old woman with a pulmonary artery sling who was misdiagnosed as having childhood-onset refractory asthma for approximately 20 years. The use of computed tomography may be useful for diagnosing this rare condition.
June 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28580744/management-of-severe-asthma-targeting-the-airways-comorbidities-and-risk-factors
#19
Peter G Gibson, Vanessa M McDonald
Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out...
June 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28569072/the-role-of-oral-methotrexate-as-a-steroid-sparing-agent-in-refractory-eosinophilic-asthma
#20
David Bilocca, B Hargadon, I D Pavord, R H Green, C E Brightling, P Bradding, A J Wardlaw, N Martin, A C Murphy, S Siddiqui
The use of oral methotrexate for refractory eosinophilic asthma in a tertiary asthma referral centre, Glenfield Hospital, Leicester, was evaluated between January 2006 and December 2014. The patients ( n = 61) were carefully phenotyped at baseline with markers of airway inflammation. In addition, a structured oral methotrexate proforma was utilized to evaluate response to therapy and adverse events. Oral steroid withdrawal was attempted 3 months after commencing treatment. Several outcomes were evaluated at 12 months, including both efficacy and adverse effects; 15% ( n = 9/61) responded by achieving a decrease in daily oral corticosteroid dose (mean 8...
January 1, 2017: Chronic Respiratory Disease
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