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Asthma small airway disease

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https://www.readbyqxmd.com/read/29769273/genome-wide-posttranscriptional-dysregulation-by-micrornas-in-human-asthma-as-revealed-by-frac-seq
#1
Rocio T Martinez-Nunez, Hitasha Rupani, Manuela Platé, Mahesan Niranjan, Rachel C Chambers, Peter H Howarth, Tilman Sanchez-Elsner
MicroRNAs are small noncoding RNAs that inhibit gene expression posttranscriptionally, implicated in virtually all biological processes. Although the effect of individual microRNAs is generally studied, the genome-wide role of multiple microRNAs is less investigated. We assessed paired genome-wide expression of microRNAs with total (cytoplasmic) and translational (polyribosome-bound) mRNA levels employing subcellular fractionation and RNA sequencing (Frac-seq) in human primary bronchoepithelium from healthy controls and severe asthmatics...
May 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29751150/lipid-mediator-leukotriene-d-4-induces-airway-epithelial-cells-proliferation-through-egfr-erk1-2-pathway
#2
Neeraj Dholia, Umesh C S Yadav
BACKGROUND: Cysteinyl leukotrienes (CysLTs), the potent lipid inflammatory mediators, are elevated in many pathological conditions and implicated in various inflammatory diseases including asthma, however their role in airway epithelial cells modulation is not clearly understood. We have investigated the effects of a CysLT, Leukotriene D4 (LTD4 ) on human airway epithelial cells, and assessed its role and mode of action in these cells. METHODOLOGY: Human small airway epithelial cells (SAECs) and A549 cells were incubated with different concentrations of LTD4 for different time intervals...
May 8, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29739850/small-molecule-targeting-of-the-stat5-6-src-homology-2-sh2-domains-to-inhibit-allergic-airway-disease
#3
J Morgan Knight, Pijus Mandal, Pietro Morlacchi, Garbo Mak, Evan Li, Matthew Madison, Cameron Landers, Brandon Saxton, Ed Felix, Brian Gilbert, Joel Sederstrom, Atul Varadhachary, Melissa M Singh, Dev Chatterjee, David B Corry, John S McMurray
Asthma is a chronic inflammatory disease of the lungs and airways and one of the most burdensome of all chronic maladies. Previous studies have established that expression of experimental and human asthma requires the IL-4/IL-13/IL-4 receptor alpha (IL-4Rα) signaling pathway, which activates the transcription factor STAT6. However, no small molecules targeting this important pathway are currently in clinical development. To this end, using a preclinical asthma model, we sought to develop and test a small-molecule inhibitor of the Src homology 2 domains in mouse and human STAT6...
May 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29729548/pepducins-as-a-potential-treatment-strategy-for-asthma-and-copd
#4
REVIEW
Reynold A Panettieri, Tonio Pera, Stephen B Liggett, Jeffrey L Benovic, Raymond B Penn
Current therapies to treat asthma and other airway diseases primarily include anti-inflammatory agents and bronchodilators. Anti-inflammatory agents target trafficking and resident immunocytes and structural cells, while bronchodilators act to prevent or reverse shortening of airway smooth muscle (ASM), the pivotal tissue regulating bronchomotor tone. Advances in our understanding of the biology of G protein-coupled receptors (GPCRs) and biased agonism offers unique opportunities to modulate GPCR function that include the use of pepducins and allosteric modulators...
May 2, 2018: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29728508/small-molecule-mimetics-of-%C3%AE-helical-domain-of-irak2-attenuate-the-proinflammatory-effects-of-il-33-in-asthma-like-mouse-models
#5
Jinghong Li, Kunio Saruta, Justin P Dumouchel, Jenna M Magat, Joanna L Thomas, Dariush Ajami, Mitra Rebek, Julius Rebek, Timothy D Bigby
IL-33 and its receptor ST2 play important roles in airway inflammation and contribute to asthma onset and exacerbation. The IL-33/ST2 signaling pathway recruits adapter protein myeloid differentiation primary response 88 (MyD88) to transduce intracellular signaling. MyD88 forms a complex with IL-R-associated kinases (IRAKs), IRAK4 and IRAK2, called the Myddosome (MyD88-IRAK4-IRAK2). The myddosome subsequently activates downstream NF-κB and MAPKs p38 and JNK. We established an asthma-like mouse model by intratracheal administration of IL-33...
May 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29676068/trpv1-blocking-alleviates-airway-inflammation-and-remodeling-in-a-chronic-asthma-murine-model
#6
Joon Young Choi, Hwa Young Lee, Jung Hur, Kyung Hoon Kim, Ji Young Kang, Chin Kook Rhee, Sook Young Lee
PURPOSE: Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. There is emerging interest in the involvement of the transient receptor potential vanilloid 1 (TRPV1) channel in the pathophysiology of asthma. This study examined whether TRPV1 antagonism alleviates asthma features in a murine model of chronic asthma. METHODS: BALB/c mice were sensitized to and challenged by ovalbumin to develop chronic asthma...
May 2018: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/29627118/alveolar-and-bronchial-nitric-oxide-in-chronic-obstructive-pulmonary-disease-and-asthma-copd-overlap
#7
Bernardino Alcázar-Navarrete, Francisca Castellano Miñán, Pablo Santiago Díaz, Oliveiro Ruiz Rodríguez, Pedro J Romero Palacios
INTRODUCTION: Exhaled nitric oxide (FENO ) measurements differentiate COPD phenotypes from asthma-COPD overlap (ACO). To date, no study has been conducted to determine whether alveolar and bronchial components differ in this group of patients. METHODS: This was an observational cross-sectional study recruiting ambulatory COPD patients. FENO was measured, differentiating alveolar (CANO ) from bronchial (JawNO ) components using a multiple-flow technique. CANO and JawNO values were compared between eosinophilic COPD patients (defined as ≥ 300 eosinophils/μL in peripheral blood test, or ≥ 2% eosinophils or ≥ 3% eosinophils), and a linear regression analysis was performed to determine clinical and biological variables related to these measurements...
April 4, 2018: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/29626633/serum-lipoproteins-are-not-associated-with-the-severity-of-asthma
#8
Federica Scaduto, Rosaria Vincenza Giglio, Alida Benfante, Dragana Nikolic, Giuseppe Montalto, Manfredi Rizzo, Nicola Scichilone
BACKGROUND: Asthma is a chronic inflammatory disorder of the bronchi with a complicated and largely unknown pathogenesis. In this context, an emerging role is attributed to the apolipoproteins which serve as structural components of plasma lipoproteins. Low density lipoproteins (LDL) may be involved in the inflammatory pathways of the asthmatic airways; in particular, small dense LDL (sdLDL) particles were associated with increased oxidative susceptibility compared to medium and large sized LDL...
April 4, 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29611767/impulse-oscillometry-and-nitrogen-washout-test-in-the-assessment-of-small-airway-dysfunction-in-asthma-correlation-with-quantitative-computed-tomography
#9
Leonello Fuso, Giuseppe Macis, Carola Condoluci, Martina Sbarra, Chiara Contu, Emanuele G Conte, Giulia Angeletti, Paolo Montuschi
OBJECTIVE: Small airway dysfunction (SAD) and airway remodeling influence the disease control and progression in asthma. We investigated whether impulse oscillometry (IOS) and single breath nitrogen washout (SBN2 W) could be reliable tests in evaluating SAD and airway remodeling by correlating their data with radiological parameters derived from quantitative chest multidetector computed tomography (MDCT) imaging. METHODS: Lung function tests were performed before and after bronchodilator...
April 3, 2018: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/29604272/resistin-upregulates-muc5ac-b-mucin-gene-expression-in-human-airway-epithelial-cells
#10
Soyoung Kwak, Yong-Dae Kim, Hyung Gyun Na, Chang Hoon Bae, Si-Youn Song, Yoon Seok Choi
Adipokines, a group of proteins including leptin, visfatin, resistin, and adiponectin, are produced by adipocytes. Among adipokines, resistin is implicated in insulin resistance and inflammatory response modulation. Mucus hypersecretion has been greatly linked to airway diseases, such as asthma, chronic obstructive pulmonary disease, and rhinosinusitis. Increasing evidence has indicated that adipokines, such as leptin and visfatin, play important regulatory roles in various biological processes involved in mucus secretion...
March 28, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29467201/small-airways-dysfunction-the-link-between-allergic-rhinitis-and-allergic-asthma
#11
Amaryllis Haccuria, Alain Van Muylem, Andrei Malinovschi, Vi Doan, Alain Michils
Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in small airways have been found in asthma. If the "one airway, one disease" concept is consistent, such dysfunctions should also be detected in the peripheral airways of patients suffering from allergic rhinitis.We investigated whether peripheral airway reactivity and NO overproduction could be documented in distal airways in patients with allergic rhinitis. Exhaled NO fraction ( F eNO ) and the slope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfur hexafluoride (SF6 ) were measured in 31 patients with allergic asthma, 23 allergic rhinitis patients and 24 controls, before and after sputum induction...
February 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29438818/small-and-large-airway-reactions-to-osmotic-stimuli-in-asthma-and-chronic-idiopathic-cough
#12
Ewa-Lena Johansson, Ewa Ternesten-Hasséus, Per Gustafsson, Teet Pullerits, Monica Arvidsson, Eva Millqvist
BACKGROUND: Chronic cough is a common symptom and related to several pulmonary, airway and heart diseases. When all likely medical explanations for the coughing are excluded, there remains a large group of patients with chronic coughing, which is mostly a cough reflex easily triggered by environmental irritants and noxious stimuli. The main aim of this study was to improve the diagnostic ability to differentiate chronic idiopathic cough (CIC) from asthma. METHODS: Twenty-three patients with CIC, 16 patients with mild asthma and 21 control participants were included...
April 2018: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29427981/environmental-causes-of-asthma
#13
Donald W Cockcroft
Environmental factors which cause asthma are those that induce airway inflammation with eosinophils (more common) or neutrophils along with airway hyperresponsiveness (AHR). The most common of these (indeed the most common cause of asthma) are IgE-mediated inhalant allergen exposures. Allergen-induced AHR and inflammation are both associated with the allergen-induced late asthmatic response (LAR). Although allergens were previously recognized only as causes of symptoms and bronchoconstriction in asthmatics, we now appreciate them as causes of the fundamental pathophysiologic features of asthma...
February 2018: Seminars in Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29423947/the-effects-of-a-ccr3-inhibitor-axp1275-on-allergen-induced-airway-responses-in-adults-with-mild-to-moderate-atopic-asthma
#14
G M Gauvreau, J M FitzGerald, L P Boulet, R M Watson, L Hui, H Villineuve, T X Scime, A R Schlatman, C Obminski, J Kum, S Boehme, T W Ly, K B Bacon, P M O'Byrne
BACKGROUND: CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. OBJECTIVE: This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. METHODS: Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind cross-over study to compare early and late allergen-induced asthmatic responses, methacholine PC20 , blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo...
April 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29411860/self-management-for-bronchiectasis
#15
REVIEW
Carol Kelly, Seamus Grundy, Dave Lynes, David Jw Evans, Sharada Gudur, Stephen J Milan, Sally Spencer
BACKGROUND: Bronchiectasis is a long term respiratory condition with an increasing rate of diagnosis. It is associated with persistent symptoms, repeated infective exacerbations, and reduced quality of life, imposing a burden on individuals and healthcare systems. The main aims of therapeutic management are to reduce exacerbations and improve quality of life. Self-management interventions are potentially important for empowering people with bronchiectasis to manage their condition more effectively and to seek care in a timely manner...
February 7, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29400694/all-plugged-up-noninvasive-mucus-score-to-assess-airway-dysfunction-in-asthma
#16
Steve N Georas
Asthma is remarkably heterogeneous, and there are multiple underlying inflammatory pathways and structural airway abnormalities that lead to symptomatic disease. Consequently, a current challenge in the field is to precisely characterize different types of asthma, with the goal of developing personalized approaches to therapy. In the current issue of the JCI, Dunican et al. developed a noninvasive way to assess airway dysfunction in asthma by measuring mucus accumulation using multidetector computed tomography (MDCT) and found that mucus plugging of small airways was remarkably common in subjects with severe asthma...
March 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29368419/utility-of-single-versus-multiple-breath-washout-in-adult-asthma
#17
S Kjellberg, E Viklund, P D Robinson, O Zetterström, A-C Olin, P Gustafsson
Nitrogen multiple breath washout (N2 MBW) is a sensitive method to identify peripheral airway involvement in asthma, but is a time-consuming test. The N2 vital capacity single breath (VC SBW) test offers greater time efficiency, but concordance with N2 MBW is poorly understood. The prevalence of peripheral airway abnormality was determined by N2 MBW and N2 SBW tests in 194 asthmatic subjects aged 18-1 years. N2 MBW data were related to findings in 400 healthy controls, aged 17-71 years, while N2 SBW data were compared to findings in 224 healthy controls, aged 15-65 years, to derive equipment-specific reference values...
January 24, 2018: Clinical Physiology and Functional Imaging
https://www.readbyqxmd.com/read/29357863/accumulation-mode-particles-and-lps-exposure-induce-tlr-4-dependent-and-independent-inflammatory-responses-in-the-lung
#18
Angela M Fonceca, Graeme R Zosky, Elizabeth M Bozanich, Erika N Sutanto, Anthony Kicic, Paul S McNamara, Darryl A Knight, Peter D Sly, Debra J Turner, Stephen M Stick
BACKGROUND: Accumulation mode particles (AMP) are formed from engine combustion and make up the inhalable vapour cloud of ambient particulate matter pollution. Their small size facilitates dispersal and subsequent exposure far from their original source, as well as the ability to penetrate alveolar spaces and capillary walls of the lung when inhaled. A significant immuno-stimulatory component of AMP is lipopolysaccharide (LPS), a product of Gram negative bacteria breakdown. As LPS is implicated in the onset and exacerbation of asthma, the presence or absence of LPS in ambient particulate matter (PM) may explain the onset of asthmatic exacerbations to PM exposure...
January 22, 2018: Respiratory Research
https://www.readbyqxmd.com/read/29354485/is-forced-oscillation-technique-the-next-respiratory-function-test-of-choice-in-childhood-asthma
#19
REVIEW
Afaf Alblooshi, Alia Alkalbani, Ghaya Albadi, Hassib Narchi, Graham Hall
Respiratory diseases, especially asthma, are common in children. While spirometry contributes to asthma diagnosis and management in older children, it has a limited role in younger children whom are often unable to perform forced expiratory manoeuvre. The development of novel diagnostic methods which require minimal effort, such as forced oscillation technique (FOT) is, therefore, a welcome and promising addition. FOT involves applying external, small amplitude oscillations to the respiratory system during tidal breathing...
December 26, 2017: World Journal of Methodology
https://www.readbyqxmd.com/read/29316647/role-of-polyamines-in-asthma-pathophysiology
#20
REVIEW
Vaibhav Jain
Asthma is a complex disease of airways, where the interactions of immune and structural cells result in disease outcomes with airway remodeling and airway hyper-responsiveness. Polyamines, which are small-sized, natural super-cations, interact with negatively charged intracellular macromolecules, and altered levels of polyamines and their interactions have been associated with different pathological conditions including asthma. Elevated levels of polyamines have been reported in the circulation of asthmatic patients as well as in the lungs of a murine model of asthma...
January 6, 2018: Medical Sciences: Open Access Journal
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