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Sean A McGhee
PURPOSE OF REVIEW: Although biologic therapies can provide outstanding efficacy in the management of lung disease, especially asthma, most of these agents have been approved only for adults. Recent findings provide new strategies for using these agents in children. RECENT FINDINGS: Extensive evidence has consistently demonstrated the efficacy and safety of biologic therapy for asthma. In addition, some studies have documented potentially important secondary effects, such as improving response to respiratory virus infection in asthmatic patients...
March 13, 2018: Current Opinion in Pediatrics
Giuseppe Brescia, Daniela Parrino, Lorenzo Nicolè, Claudia Zanotti, Cristiano Lanza, Umberto Barion, Filippo Marino, Gino Marioni
PURPOSE: The term aspirin-exacerbated respiratory disease (AERD) refers to a combination of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and acute respiratory tract reactions to nonsteroidal anti-inflammatory drugs. AERD has now been included among the CRSwNP endotypes, and is considered one of the most aggressive in terms of disease recurrence. Cortactin is a multi-domain protein with a part in several cellular mechanisms involving actin assembly and cytoskeleton arrangement...
March 5, 2018: American Journal of Otolaryngology
Xiaojing Zheng, Catherine M O'Connell, Wujuan Zhong, Uma M Nagarajan, Manoj Tripathy, De'Ashia Lee, Ali N Russell, Harold Wiesenfeld, Sharon Hillier, Toni Darville
Sexually transmitted infections with Chlamydia trachomatis and/or Neisseria gonorrhoeae and rates of pelvic inflammatory disease (PID) in women continue to rise, with reinfection being common because of poor adaptive immunity. Diagnosis remains imprecise, and pathogenesis data are derived primarily from monoinfection of mice with C. trachomatis or N. gonorrhoeae By comparing blood mRNA responses of women with C. trachomatis - and/or N. gonorrhoeae -induced PID and histologic endometritis with those from women with C...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Yoshihito Shima, Yasushi Kawaguchi, Masataka Kuwana
OBJECTIVES: To evaluate the anti-interleukin(IL)-6 receptor antibody tocilizumab (TCZ) as a treatment of systemic sclerosis (SSc), a randomized parallel group study was conducted, and compared their results and baseline cytokine/chemokine profiles. METHODS: Patients were assigned to a TCZ add-on group (TCZ group, n = 7) and a conventional therapy group (Conv group, n = 6). TCZ (8 mg/kg/month) for 6 months, and the modified Rodnan total skin score (mRSS) was used to compare the efficacy...
March 13, 2018: Modern Rheumatology
Hans Petersen, Rodrigo Vazquez Guillamet, Paula Meek, Akshay Sood, Yohannes Tesfaigzi
Chronic obstructive pulmonary disease (COPD) is a syndrome that comprises several lung pathologies, but subphenotyping the various disease subtypes has been difficult. One reason may be that current efforts which are focused on studying COPD once it has occurred do not allow to trace back the different origins of disease. This prespective proposes that emphysema originates when susceptible airway, endothelial, and/or hematopoietic cells are exposed to environmental toxins, such as cigarette smoke, biomass fuel, or traffic emissions...
March 9, 2018: American Journal of Respiratory Cell and Molecular Biology
Ghislaine Annie C Isabwe, Marlene Garcia Neuer, Leticia de Las Vecillas Sanchez, Donna-Marie Lynch, Kathleen Marquis, Mariana Castells
BACKGROUND: The increasing use of monoclonal antibodies (mAbs) has led to a rise in hypersensitivity reactions (HSRs), which prevent their use as first-line therapy. HSRs symptoms, diagnostic tools and directed management approaches have not been standardized. OBJECTIVE: We propose a novel evidence-based classification of HSRs to mAbs, based on the clinical phenotypes, underlying endotypes and biomarkers; as well as their management with desensitization. METHODS: Phenotypes, endotypes and biomarkers of HSRs to 16 mAbs for 104 patients were described and compared to the outcomes of 526 subcutaneous and intravenous desensitizations...
March 5, 2018: Journal of Allergy and Clinical Immunology
J Kenneth Baillie, Andrew Bretherick, Christopher S Haley, Sara Clohisey, Alan Gray, Lucile P A Neyton, Jeffrey Barrett, Eli A Stahl, Albert Tenesa, Robin Andersson, J Ben Brown, Geoffrey J Faulkner, Marina Lizio, Ulf Schaefer, Carsten Daub, Masayoshi Itoh, Naoto Kondo, Timo Lassmann, Jun Kawai, Damian Mole, Vladimir B Bajic, Peter Heutink, Michael Rehli, Hideya Kawaji, Albin Sandelin, Harukazu Suzuki, Jack Satsangi, Christine A Wells, Nir Hacohen, Thomas C Freeman, Yoshihide Hayashizaki, Piero Carninci, Alistair R R Forrest, David A Hume
Genetic variants underlying complex traits, including disease susceptibility, are enriched within the transcriptional regulatory elements, promoters and enhancers. There is emerging evidence that regulatory elements associated with particular traits or diseases share similar patterns of transcriptional activity. Accordingly, shared transcriptional activity (coexpression) may help prioritise loci associated with a given trait, and help to identify underlying biological processes. Using cap analysis of gene expression (CAGE) profiles of promoter- and enhancer-derived RNAs across 1824 human samples, we have analysed coexpression of RNAs originating from trait-associated regulatory regions using a novel quantitative method (network density analysis; NDA)...
March 1, 2018: PLoS Computational Biology
James D Chalmers, Sanjay H Chotirmall
European Respiratory Society guidelines for the management of adult bronchiectasis highlight the paucity of treatment options available for patients with this disorder. No treatments have been licensed by regulatory agencies worldwide, and most therapies used in clinical practice are based on very little evidence. Development of new treatments is needed urgently. We did a systematic review of scientific literature and clinical trial registries to identify agents in early-to-late clinical development for bronchiectasis in adults...
February 22, 2018: Lancet Respiratory Medicine
Gailen D Marshall
No abstract text is available yet for this article.
February 23, 2018: Expert Opinion on Biological Therapy
Justin H Turner, Rakesh K Chandra, Ping Li, Kemberlee Bonnet, David G Schlundt
No abstract text is available yet for this article.
February 13, 2018: Journal of Allergy and Clinical Immunology
Devyani Lal, Claire Hopkins, Rohit D Divekar
BACKGROUND: Endotypic and prognosticating features of chronic rhinosinusitis without nasal polyposis (CRSsNP) are poorly understood. Our objectives were to use an unbiased symptom-based approach to: (1) study symptoms, clinical and endotypic features; and (2) identify features predicating outcomes from endoscopic sinus surgery (ESS). METHODS: Clinical, computed tomography (CT), histopathology, and 22-item Sino-Nasal Outcome Test (SNOT-22) data was collected on 146 adult CRSsNP patients who underwent ESS...
February 13, 2018: International Forum of Allergy & Rhinology
Hui Fang Lim, Parameswaran Nair
Severe asthma is a complex disease consisting of different endotypes with different inflammatory and clinicopathological characteristics due to the heterogeneity of immune responses and smooth muscle dysfunction. There is an unmet clinical need to develop and to validate biomarkers that can differentiate between the asthma endotypes and guide clinical management, particularly since the availability of biologicals directed against T2 cytokines. The presence of a "Th2 endotype" is currently assessed in clinical practice using markers, such as eosinophil count in sputum or blood, fraction of exhaled nitric oxide, and immunoglobulin E...
February 2018: Seminars in Respiratory and Critical Care Medicine
Samuel N Uwaezuoke, Adaeze C Ayuk, Joy N Eze
Severe asthma or therapy-resistant asthma in children is a heterogeneous disease that affects all age-groups. Given its heterogeneity, precision in diagnosis and treatment has become imperative, in order to achieve better outcomes. If one is thus able to identify specific patient phenotypes and endotypes using the appropriate biomarkers, it will assist in providing the patient with more personalized and appropriate treatment. However, there appears to be a huge diagnostic gap in severe asthma, as there is no single test yet that accurately determines disease phenotype...
2018: Journal of Asthma and Allergy
Mary Grace Baker, Hugh A Sampson
No abstract text is available yet for this article.
March 2018: Annals of Allergy, Asthma & Immunology
Shangyong Li, Linna Wang, Xuehong Chen, Wenwen Zhao, Mi Sun, Yantao Han
Alginate, the most abundant carbohydrate presents in brown macroalgae, has recently gained increasing attention as an alternative biomass for the production of biofuel. Oligoalginate lyases catalyze the degradation of alginate oligomers into monomers, a prerequisite for bioethanol production. In this study, two new oligoalginate lyase genes, oalC6 and oalC17, were cloned from Cellulophaga sp. SY116, and expressed them in Escherichia coli. The deduced oligoalginate lyases, OalC6 and OalC17, belonged to the polysaccharide lyase (PL) family 6 and 17, respectively...
January 24, 2018: Marine Biotechnology
B Liao, J-X Liu, Z-Y Li, Z Zhen, P-P Cao, Y Yao, X-B Long, H Wang, Y Wang, R Schleimer, Z Liu
BACKGROUND: The expression of chronic rhinosinusitis (CRS) is multidimensional. Disease heterogeneity in patients with CRS remains poorly understood. This study aimed to identify endotypes of CRS using cluster analysis by integrating multidimensional characteristics and to explore their association with treatment outcomes. METHODS: A total of 28 clinical variables and 39 mucosal cellular and molecular variables were analyzed using principal component analysis. Cluster analysis was performed on 246 prospectively recruited Chinese CRS patients with at least 1-year postoperative follow-up...
January 13, 2018: Allergy
Vladimir Fijačko, Marina Labor, Mirjana Fijačko, Sanda Škrinjarić-Cincar, Slavica Labor, Iva Dumbović Dubravčić, Tatjana Bačun, Aleksandar Včev, Sanja Popović-Grle, Davor Plavec
BACKGROUND: No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients. METHODS: A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium)...
January 10, 2018: Wiener Klinische Wochenschrift
Gilda Varricchi, Giancarlo Marone, Giuseppe Spadaro, Michele Russo, Francescopaolo Granata, Arturo Genovese, Gianni Marone
Asthma is a heterogeneous disease characterized by chronic airway inflammation that results in a wide spectrum of clinical manifestations. Patients with severe asthma represent a substantial share of consumption of healthcare resources and hospitalization. Moreover, these patients are at risk of increased morbidity and mortality. Recently, several phenotypes and endotypes of asthma have been identified. The identification of specific subtypes of asthma is fundamental for optimizing the clinical benefit of novel treatments...
January 9, 2018: Current Medicinal Chemistry
Milena Sokolowska, Remo Frei, Nonhlanhla Lunjani, Cezmi A Akdis, Liam O'Mahony
The mucosal immune system is in constant communication with the vast diversity of microbes present on body surfaces. The discovery of novel molecular mechanisms, which mediate host-microbe communication, have highlighted the important roles played by microbes in influencing mucosal immune responses. Dendritic cells, epithelial cells, ILCs, T regulatory cells, effector lymphocytes, NKT cells and B cells can all be influenced by the microbiome. Many of the mechanisms being described are bacterial strain- or metabolite-specific...
2018: Asthma research and practice
Gino Marioni, Claudia Zanotti, Giuseppe Brescia
BACKGROUND: The recently reported prevalence of chronic rhinosinusitis (CRS) among people >60 years old was 4.7%, with CRS emerging as the sixth most common chronic condition in the elderly. There is still a dearth of studies that focused on older patients, however, regarding the characteristics of CRS with nasal polyps (CRSwNP). OBJECTIVE: The emerging role of CRSwNP endotyping to enable a tailored medical approach (for elderly patients also) was investigated...
January 1, 2018: Allergy and Asthma Proceedings:
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