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Difficult to treat asthma

Marieke Verkleij, Anita Beelen, Bart E van Ewijk, Rinie Geenen
OBJECTIVE: For children with problematic severe asthma, achieving adequate control of asthma is difficult. The aim of this prospective observational study was to evaluate the effects of intensive multidisciplinary inpatient treatment on multiple outcome variables in children with problematic severe asthma. METHODS: Participants were 89 children with problematic severe asthma (mean age 13.6 ± 2.5 years) treated in tertiary care clinics at high altitude (Switzerland) or sea level (Netherlands) and their parents (85 mothers, 55 fathers)...
October 13, 2016: Pediatric Pulmonology
R Ragesh, Animesh Ray, Agrima Mian, Surabhi Vyas, S K Sharma
We describe an interesting case of severe asthma who was not showing satisfactory response to standard treatment. Investigations revealed him to be suffering from allergic bronchopulmonary aspergillosis (ABPA). After starting systemic steroids he showed marked improvement initially only to have recurrent symptoms within a year. He was investigated further and found to have chronic pulmonary aspergillosis in the form of chronic cavitary pulmonary aspergillosis (CCPA) and aspergilloma as also the presence of selective IgA deficiency...
April 2016: Journal of the Association of Physicians of India
Jantina C de Groot, Huib Storm, Marijke Amelink, Selma B de Nijs, Edwin Eichhorn, Bennie H Reitsma, Elisabeth H D Bel, Anneke Ten Brinke
Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0...
April 2016: ERJ Open Research
Steven W Yancey, Hector G Ortega, Oliver N Keene, Bhabita Mayer, Necdet B Gunsoy, Christopher E Brightling, Eugene R Bleecker, Pranabashis Haldar, Ian D Pavord
BACKGROUND: Studies show that mepolizumab can reduce the frequency of clinically significant exacerbations in patients with severe eosinophilic asthma, compared with placebo. However, important events such as hospitalizations and emergency room visits are rare and difficult to characterize in single studies. OBJECTIVE: We sought to compare hospitalization or hospitalization and/or emergency room visit rates in patients with severe eosinophilic asthma treated with mepolizumab or placebo in addition to standard of care for at least 24 weeks...
October 4, 2016: Journal of Allergy and Clinical Immunology
Amy Chang, Ynuk Bossé
Asthma is a lung disorder triggered by various airborne factors in susceptible individuals. Although generally controlled, asthma can be severe and difficult to treat. Presently, increasing numbers of pharmaceuticals capable of blocking or mimicking specific endogenous molecules are undergoing clinical trials in asthmatic individuals whose symptoms are poorly controlled despite adherence to guideline therapies. Unfortunately, only a few, meticulously selected patients have been found to minimally benefit. These findings not only confirm that the molecular pathogenesis of severe asthma is variable between patients but also suggest that each molecular defect is likely to contribute little on its own in each patient...
September 28, 2016: Trends in Molecular Medicine
Elena Priante, Laura Moschino, Veronica Mardegan, Paolo Manzoni, Sabrina Salvadori, Eugenio Baraldi
Despite notable advances in the survival and management of preterm infants in recent decades, chronic lung disease remains a common complication. Approximately one in three infants born preterm (< 32 weeks of gestation) are hospitalized with respiratory problems (mainly due to infections) in their first 2 years of life, and the risk of childhood wheezing is three times higher in this population. By comparison with infants born at term, there seems to be a higher incidence of respiratory morbidity in those born preterm, even in the absence of bronchopulmonary dysplasia (BPD) and in late-preterm babies...
September 2016: American Journal of Perinatology
Maartje Willeboordse, Kim D G van de Kant, Charlotte A van der Velden, Constant P van Schayck, Edward Dompeling
BACKGROUND: Asthma and obesity are highly prevalent in children, and are interrelated resulting in a difficult-to-treat asthma-obesity phenotype. The exact underlying mechanisms of this phenotype remain unclear, but decreased physical activity (PA) could be an important lifestyle factor. We hypothesize that both asthma and overweight/obesity decrease PA levels and interact on PA levels in asthmatic children with overweight/obesity. METHODS: School-aged children (n = 122) were divided in 4 groups (healthy control, asthma, overweight/obesity and asthma, and overweight/obesity)...
2016: BMC Public Health
Wouter H van Geffen, W R Douma, Dirk Jan Slebos, Huib A M Kerstjens
BACKGROUND: Bronchodilators are a central component for treating exacerbations of chronic obstructive pulmonary disease (COPD) all over the world. Clinicians often use nebulisers as a mode of delivery, especially in the acute setting, and many patients seem to benefit from them. However, evidence supporting this choice from systematic analysis is sparse, and available data are frequently biased by the inclusion of asthma patients. Therefore, there is little or no formal guidance regarding the mode of delivery, which has led to a wide variation in practice between and within countries and even among doctors in the same hospital...
2016: Cochrane Database of Systematic Reviews
Tao Lin, Junbin Liu, Shuhua Yang, Xianzhe Liu, Xiaobo Feng, Dehao Fu
BACKGROUND: There has been a recent increase in the number of patients suffering from bone and joint diseases, as a consequence of corticosteroids administration. There are more patients treated with low dose of GCs under long-term conditions in clinical, such as effect of GCs on Rheumatoid arthritis, Crohn's disease and Asthma patients. Hence, it was difficult for doctor to determine which problem occur first - OP or ON; however, there was no clinical report previously in the literature, and there was no effective animal model of OP and ON about low dose GCs...
July 2016: Indian Journal of Orthopaedics
N Radhakrishna, T R Tay, F Hore-Lacy, R Hoy, E Dabscheck, M Hew
AIM: We determined the proportion of asthma patients under specialist care who remain difficult-to-treat and might benefit from systematic assessment. We additionally report the characteristics and indications for referral in 90 patients who received systematic assessment for difficult asthma. METHODS: We conducted a three-month prospective audit of our hospital's general asthma clinic. We then analyzed consecutive patients over 18 months referred on for systematic assessment of difficult asthma...
August 2016: Respiratory Medicine
Kai Fruth, Jan Gosepath
Aspirin exacerbated respiratory disease (AERD) has been defined as a non-steroidal anti-inflammatory drug (NSAID)-triggered hypersensitivity, non-allergic bronchial asthma and chronic rhinosinusitis (CRS) with nasal polyps. The underlying pathophysiology of AERD is not completely understood so far. An altered arachidonic acid metabolism and dysregulated enzyme activity are regarded to be causal. AERD is characterized by recalcitrant CRS with recurrent nasal polyps after sinus surgery, accompanied by difficult to treat bronchial asthma and adverse reaction after NSAID ingestion such as nasal blockage, itching, laryngospasm and severe asthma attacks...
2016: Advances in Oto-rhino-laryngology
Erin D Gordon, Laura J Simpson, Cydney L Rios, Lando Ringel, Marrah E Lachowicz-Scroggins, Michael C Peters, Agata Wesolowska-Andersen, Jeanmarie R Gonzalez, Hannah J MacLeod, Laura S Christian, Shaopeng Yuan, Liam Barry, Prescott G Woodruff, K Mark Ansel, Karl Nocka, Max A Seibold, John V Fahy
Type 2 inflammation occurs in a large subgroup of asthmatics, and novel cytokine-directed therapies are being developed to treat this population. In mouse models, interleukin-33 (IL-33) activates lung resident innate lymphoid type 2 cells (ILC2s) to initiate airway type 2 inflammation. In human asthma, which is chronic and difficult to model, the role of IL-33 and the target cells responsible for persistent type 2 inflammation remain undefined. Full-length IL-33 is a nuclear protein and may function as an "alarmin" during cell death, a process that is uncommon in chronic stable asthma...
August 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
Linda Rogers
Gastroesophageal reflux and obstructive sleep apnea syndrome are conditions that practitioners have been encouraged to evaluate and treat as part of a comprehensive approach to achieving asthma control. In this review, the author looks at the evidence linking these two conditions as factors that may impact difficult-to-control asthma and looks critically at the evidence suggesting that evaluation and treatment of these conditions when present impacts asthma control.
August 2016: Immunology and Allergy Clinics of North America
Sumit Bose, Leslie C Grammer, Anju T Peters
Chronic rhinosinusitis (CRS) is a persistent inflammatory disease that affects a multitude of people worldwide. The pathogenesis of CRS involves many factors including genetics, status of the sinonasal microbiome, infections, and environmental influences. Comorbidities associated with CRS include asthma, allergic rhinitis, bronchiectasis, and certain kinds of immunodeficiency. CRS can be divided into different subtypes based on endotypes and phenotypes. Infectious CRS is one such category. The etiology of infectious CRS is usually secondary to chronic bacterial infection that commonly begins with a viral upper respiratory tract infection...
July 2016: Journal of Allergy and Clinical Immunology in Practice
Mario Cazzola, Paola Rogliani
The association of asthma and chronic obstructive pulmonary disease (COPD) in the same patient, which is designated as mixed asthma-COPD phenotype or overlap syndrome (ACOS), remains a controversial issue. This is primarily because many conflicting aspects in the definition of ACOS remain, and it is extremely difficult to summarize the distinctive features of this syndrome. Furthermore, we are realizing that asthma, COPD, and ACOS are not single diseases but rather syndromes consisting of several endotypes and phenotypes and, consequently, comprising a spectrum of diseases...
June 4, 2016: Journal of Allergy and Clinical Immunology
Peter J Barnes
Multiple kinases play a critical role in orchestrating the chronic inflammation and structural changes in the respiratory tract of patients with asthma and chronic obstructive pulmonary disease (COPD). Kinases activate signaling pathways that lead to contraction of airway smooth muscle and release of inflammatory mediators (such as cytokines, chemokines, growth factors) as well as cell migration, activation, and proliferation. For this reason there has been great interest in the development of kinase inhibitors as anti-inflammatory therapies, particular where corticosteroids are less effective, as in severe asthma and COPD...
July 2016: Pharmacological Reviews
Renata Rubinsztajn, Ryszarda Chazan
Asthma is a heterogeneous inflammatory disease. Most patients respond to current standard of care, i.e., bronchodilators, inhaled glucocorticosteroids and other anti-inflammatory drugs, but in some adequate asthma control cannot be achieved with standard treatments. These difficult-to-treat patients would be the target population for new biological therapies. At present, omalizumab is the only biological agent approved for the treatment of early-onset, severe IgE-dependent asthma. It is safe, effective, and well tolerated...
2016: Advances in Experimental Medicine and Biology
Sebastian Stentzel, Andrea Teufelberger, Maria Nordengrün, Julia Kolata, Frank Schmidt, Koen van Crombruggen, Stephan Michalik, Jana Kumpfmüller, Sebastian Tischer, Thomas Schweder, Michael Hecker, Susanne Engelmann, Uwe Völker, Olga Krysko, Claus Bachert, Barbara M Bröker
BACKGROUND: A substantial subgroup of asthmatic patients have "nonallergic" or idiopathic asthma, which often takes a severe course and is difficult to treat. The cause might be allergic reactions to the gram-positive pathogen Staphylococcus aureus, a frequent colonizer of the upper airways. However, the driving allergens of S aureus have remained elusive. OBJECTIVE: We sought to search for potentially allergenic S aureus proteins and characterize the immune response directed against them...
May 10, 2016: Journal of Allergy and Clinical Immunology
Adeeb Bulkhi, Farnaz Tabatabaian, Thomas B Casale
Asthma is a complex disease where many patients remain symptomatic despite guideline-directed therapy. This suggests an unmet need for alternative treatment approaches. Understanding the physiological role of muscarinic receptors and the parasympathetic nervous system in the respiratory tract will provide a foundation of alternative therapeutics in asthma. Currently, several long-acting muscarinic antagonists (LAMAs) are on the market for the treatment of respiratory diseases. Many studies have shown the effectiveness of tiotropium, a LAMA, as add-on therapy in uncontrolled asthma...
July 2016: Drugs
Zhonghua Zhang, Jocelyn M Biagini Myers, Eric B Brandt, Patrick H Ryan, Mark Lindsey, Rachael A Mintz-Cole, Tiina Reponen, Stephen J Vesper, Frank Forde, Brandy Ruff, Stacey A Bass, Grace K LeMasters, David I Bernstein, James Lockey, Alison L Budelsky, Gurjit K Khurana Hershey
BACKGROUND: Allergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity. OBJECTIVE: We sought to determine the mechanism by which fungi affect asthma development and severity. METHODS: We integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity...
April 20, 2016: Journal of Allergy and Clinical Immunology
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