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Asthma small airway disease

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
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...
February 10, 2018: Pulmonary Pharmacology & Therapeutics
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
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...
February 9, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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
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...
February 5, 2018: Journal of Clinical Investigation
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
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
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
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
S Diver, R J Russell, C Brightling
Asthma is a common chronic inflammatory condition of the airways affecting over 300 million people worldwide. In 5-10% of cases it is severe, with disproportionate healthcare resource utilisation including costs associated with frequent exacerbations and the long-term health effects of systemic steroids. Characterisation of inflammatory pathways in severe asthma has led to development of targeted biological and small molecule therapies which aim to achieve disease control whilst minimising corticosteroid-associated morbidity...
January 8, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Karl Deacon, Alan J Knox
Airway smooth muscle (ASM) cells contribute to asthmatic lung pathology with chemokine hypersecretion and increased ASM cell mass. With little recent progress in the development of asthma therapies, a greater understanding of lung inflammation mechanisms has become a priority. Chemokine gene expression in ASM cells is dependent upon NF-κB transcription factor activity. The telomerase/shelterin complex maintains chromosomal telomere ends during cell division. Telomerase is a possible cofactor for NF-κB activity, but its role in NF-κB activity in airway tissue inflammation is not known...
January 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Alicja Pacholewska, Matthias F Kraft, Vincent Gerber, Vidhya Jagannathan
MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression analysis...
December 12, 2017: Genes
Claire A Cox, Ilse M Boudewijn, Sebastiaan J Vroegop, Siebrig Schokker, Anne J Lexmond, Henderik W Frijlink, Paul Hagedoorn, Judith M Vonk, Martijn P Farenhorst, Nick H T Ten Hacken, Huib A M Kerstjens, Dirkje S Postma, Maarten van den Berge
BACKGROUND: Smoking is as prevalent in asthmatics as in the general population. Asthmatic smokers benefit less from inhaled corticosteroids (ICS) than non-smoking asthmatics, possibly due to more smoking-induced small airways disease. Thus targeting small airways may be important in treating asthmatic (ex-)smokers. We hypothesized that extrafine particle ICS improve small airways function more than non-extrafine particle ICS in asthmatic (ex-)smokers. METHODS: We performed an open-label, randomized, three-way cross-over study comparing extrafine beclomethasone (HFA-QVAR) to non-extrafine beclomethasone (HFA-Clenil) and fluticasone (HFA-Flixotide) in 22 smokers and 21 ex-smokers with asthma (?5 packyears)...
September 2017: Respiratory Medicine
Per Thunqvist, Ellen Tufvesson, Leif Bjermer, Anna Winberg, Vineta Fellman, Magnus Domellöf, Erik Melén, Mikael Norman, Jenny Hallberg
BACKGROUND AND OBJECTIVES: Follow-up studies of children and young adults born very-to-moderately preterm show persistent and significant lung function deficits. The aim of the study was to determine lung function and airway mechanics in school-aged children born in 2004 to 2007 and extremely preterm (after 22-26 weeks of gestation). METHODS: In a population-based cohort of children born extremely preterm and controls born at term (n = 350), follow-up at 6½-years-of-age was performed using spirometry and impulse oscillometry...
January 2018: Pediatric Pulmonology
Lindsay R Stolzenburg, Ann Harris
Chronic respiratory diseases encompass a group of diverse conditions affecting the airways, which all impair lung function over time. They include cystic fibrosis, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and asthma, which together affect hundreds of millions of people worldwide. MicroRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional gene repression, are now recognized as major regulators in the development and progression of chronic lung disease. Alterations in miRNA abundance occur in lung tissue, inflammatory cells, and freely circulating in blood and are thought to function both as drivers and modifiers of disease...
November 27, 2017: Biological Chemistry
Huilong Chen, Xiangqin Xu, Sheng Cheng, Yuzhu Xu, Qi Xuefei, Yong Cao, Jungang Xie, Cong-Yi Wang, Yongjian Xu, Weining Xiong
Asthma is a chronic T helper type 2 (Th2) cell-mediated inflammatory disease characterized by airway hyperresponsiveness (AHR) and airway inflammation. Although the majority of patients with asthma can achieve a good level of control with existing treatments, asthma runs a chronic course and the effectiveness of current treatment is not satisfactory for certain patients. MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the post-transcriptional level; their role in regulating allergic inflammation remains largely unknown...
November 2017: Experimental and Therapeutic Medicine
Rajinder K Gupta, Poonam Soree, Koundinya Desiraju, Anurag Agrawal, Shashi Bala Singh
HAPE susceptible (HAPE-S, had HAPE episode in past) subjects may have subclinical cardio-pulmonary dysfunction. We compared the results of pulmonary function tests in 25 healthy HAPE-S non-mountaineers and 19 matched HAPE resistant (HAPE-R, no HAPE episode in past). Acute normobaric hypoxia (FIo2 0.12) was administered at sea level to confirm hypoxia intolerance in HAPE-S. Unlike HAPE-R, HAPE-S subjects had elevated baseline and post-hypoxia systolic pulmonary arterial pressures (20.9 ± 3 vs 27.3 ± 5 mm Hg during normoxia and 26...
November 2, 2017: Scientific Reports
Anne H Neerincx, Susanne J H Vijverberg, Lieuwe D J Bos, Paul Brinkman, Marc P van der Schee, Rianne de Vries, Peter J Sterk, Anke-Hilse Maitland-van der Zee
Asthma is the most common chronic disease in children, and is characterized by airway inflammation, bronchial hyperresponsiveness, and airflow obstruction. Asthma diagnosis, phenotyping, and monitoring are still challenging with currently available methods, such as spirometry, FE NO or sputum analysis. The analysis of volatile organic compounds (VOCs) in exhaled breath could be an interesting non-invasive approach, but has not yet reached clinical practice. This review describes the current status of breath analysis in the diagnosis and monitoring of pediatric asthma...
December 2017: Pediatric Pulmonology
Felix Zamora, Roy Cho, Madhuri Rao, Heidi Gibson, H Erhan Dincer
Asthma is an incurable chronic disease affecting approximately 24 million people in the United States. The hallmark features of asthma are reversible airflow obstruction, airway hyperresponsiveness, airway inflammation, bronchoconstriction, and excessive mucus secretion. Clinical symptoms include episodic or persistent breathlessness, wheezing, cough, or chest tightness/pressure. Forty-five percent of asthmatics continue to have yearly exacerbations and the disease is responsible for approximately 3,600 annual deaths...
2017: Journal of visualized surgery
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