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Introduction In mild asthma, as-needed budesonide/formoterol (BUD/FORM) reduces long-term severe exacerbation risk vs. terbutaline as-needed, with similar reduction as maintenance BUD + terbutaline as-needed. In a post-hoc analysis of SYGMA 1 (NCT02149199; OʼByrne et al. NEJM 2018;378(20):1865 – 1876) we examined the short-term risk of a severe exacerbation after a single day with various levels of reliever use, comparing terbutaline as-needed, BUD/FORM as-needed, and maintenance BUD + terbutaline as-needed.
No abstract is provided for this article.
Background Changes in the treatment of coronary artery disease both surgically and percutaneously have rendered the major randomized trials historical. Furthermore, the restrictive criteria of previous trials excluded most patients treated in daily practice. Although coronary surgery is still considered the current, evidence-based, gold-standard treatment of left main (LM) and 3-vessel coronary disease, the added benefit of drug-eluting stents has further expanded the use of percutaneous coronary intervention (PCI) beyond less complex populations in daily practice. Study Design The 1500-patient, prospective, multicenter, multinational (European and North American), randomized SYNTAX study with nested registries will enroll “all-comers.” Consecutive patients with de novo 3-vessel disease (3VD) and/or LM disease will be screened for eligibility by the Heart Team (composed of an interventionalist, a cardiac surgeon, and the study coordinator) at each site and then allocated to either (1) the randomized cohort, if comparable revascularization can be achieved by either PCI or coronary artery bypass surgery (CABG), or (2) to one of the nested registries for CABG-ineligible patients (PCI registry) or for PCI-ineligible patients (CABG registry). Randomized patients will be stratified based on LM disease and diabetes by site. The primary end point for the randomized comparison is noninferiority of major adverse cardiac and cerebral events between the 2 groups at 1 year. To adequately project the expected enrollment rate per site, a run-in phase was mandated for each site interested in participating in the trial. Both cardiothoracic and interventional cardiology departments within the same institution were asked to complete a questionnaire regarding their frequency of treatment of LM and 3VD over a retrospective 3-month period. Implications By replacing most traditional inclusion and exclusion criteria with the real-world decision between the cardiothoracic surgeon and the interventionalist, this study will define the roles of CABG and PCI using drug-eluting stents in the contemporary management of LM and 3VD. Results of the run-in phase were used by the steering committee to determine eligibility and to project enrollment for each site.
No abstract is provided for this article.
Asthma causes the unpleasant sensation of breathlessness (dyspnea) caused by airway obstruction. Patients with poor perception of airway obstruction are at risk of delay in seeking medical attention and undertreatment, which can lead to avoidable deaths. Conversely, those with heightened perception are at risk of overtreatment and iatrogenic adverse effects with reliever medications, anxiety, and unnecessary use of health care resources.We sought to review evidence about symptom misperception in asthmatic patients and how to identify and manage affected patients, particularly with regard to reliever medications.We conducted a systematic literature search for studies of perception of airway function in asthmatic patients. We searched the OVID (Medline and Medline [R] in process [PubMed]), Embase, and Adisearch/Odyssey databases, restricting our search to human studies published in English from 1990-2018, with no restrictions on age, sex, or racial origin.We found that both underperception and overperception assessed during induced bronchoconstriction or bronchodilation or during changes in airway resistance were common across all age groups and that aging, disease severity, smoking, sex, ethnicity, psychologic factors, and medication are all associated with differences in perception. Importantly, airway inflammation was associated with impaired perception and a history of severe or near-fatal asthma. We also identified knowledge gaps, such as whether an individual patient's perception varies over time and the influence perception has on patients' use of reliever medication.We found that abnormal perception of airway obstruction has important clinical implications for the management of patients with asthma.
No abstract is provided for this article.
The flutter valve is a physiotherapy device that produces oscillations and positive expiratory pressure that may help clear respiratory secretions. Its effects on airway resistance and inflammation are unknown. Objective: To evaluate the acute effects of breathing exercises with a flutter device on exhaled nitric oxide (FeNO), a marker of inflammation, and airway resistance as assessed by impulse oscillometry (IOS) in healthy subjects. Methods: 14 healthy subjects, mean age 39±9 years were enrolled in the study. Whole breath respiratory resistance at 5Hz (R5) and reactance (X5) were measured by impulse oscillometry (IOS, Jaeger, Wurzburg, Germany) and FeNO at the exhalation flow rate of 50 ml/s by chemiluminescence (Niox Flex, Aerocrine, Sweden). The measurements were performed at baseline, immediately following 30 minutes of flutter breathing (Varioraw SARL, Scandipharm Inc, Alabama, USA) and repeated using a control flutter-sham device that does not produce vibrations. Results: FeNO levels were significantly decreased after flutter breathing (26.2±21.9 and 23.5±20.6 ppb; p Conclusion: The use of a flutter device significantly decreases FeNO levels without affecting airway resistance. This may be due to improvement of the ventilation/perfusion, diffusion and clearance of NO. Further studies are required to investigate flutter breathing in patients with airway disease. Granted by FAPESP/Brazil.
Glucocorticoids are the most effective therapy available for patients with asthma. They may be administered either orally or, much more safely, by inhalation. With the recognition that airway inflammation is present even in patients with mild asthma, therapy with inhaled glucocorticoids is now recommended at a much earlier stage.1 However, despite their proved efficacy in the treatment of asthma, enthusiasm for their use has been tempered by concern about systemic side effects. Because of this concern, less effective therapies are often preferred, particularly for children.Mechanism of ActionMolecular MechanismsInhaled glucocorticoids are highly lipophilic. They rapidly enter airway cells, . . .
Current therapy for asthma is highly effective. β2-Adrenergic receptor (β2AR) agonists are the most effective bronchodilators and relax airway smooth muscle cells through increased cAMP concentrations and directly opening large conductance Ca2+ channels. β2AR may also activate alternative signaling pathways that may have detrimental effects in asthma. Glucocorticoids are the most effective anti-inflammatory treatments and switch off multiple activated inflammatory genes through recruitment of histone deacetylase-2, activating anti-inflammatory genes, and through increasing mRNA stability of inflammatory genes. There are beneficial molecular interactions between β2AR and glucocorticoid-activated pathways. Understanding these signaling pathways may lead to even more effective therapies in the future. Current therapy for asthma is highly effective. β2-Adrenergic receptor (β2AR) agonists are the most effective bronchodilators and relax airway smooth muscle cells through increased cAMP concentrations and directly opening large conductance Ca2+ channels. β2AR may also activate alternative signaling pathways that may have detrimental effects in asthma. Glucocorticoids are the most effective anti-inflammatory treatments and switch off multiple activated inflammatory genes through recruitment of histone deacetylase-2, activating anti-inflammatory genes, and through increasing mRNA stability of inflammatory genes. There are beneficial molecular interactions between β2AR and glucocorticoid-activated pathways. Understanding these signaling pathways may lead to even more effective therapies in the future.
Conference Abstract| January 01 1985 Histamine, Substance P and Neurogenic Flare in Human Skin D.J. Heavey; D.J. Heavey 1Department of Clinical Pharmacology, Royal Postgraduate Medical School, London W12 Search for other works by this author on: This Site PubMed Google Scholar R.W. Fuller; R.W. Fuller 1Department of Clinical Pharmacology, Royal Postgraduate Medical School, London W12 Search for other works by this author on: This Site PubMed Google Scholar P.J. Barnes; P.J. Barnes 1Department of Clinical Pharmacology, Royal Postgraduate Medical School, London W12 Search for other works by this author on: This Site PubMed Google Scholar C.T. Dollery C.T. Dollery 1Department of Clinical Pharmacology, Royal Postgraduate Medical School, London W12 Search for other works by this author on: This Site PubMed Google Scholar Clin Sci (Lond) (1985) 68 (s11): 23P–24P. https://doi.org/10.1042/cs068023Pb Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation D.J. Heavey, R.W. Fuller, P.J. Barnes, C.T. Dollery; Histamine, Substance P and Neurogenic Flare in Human Skin. Clin Sci (Lond) 1 January 1985; 68 (s11): 23P–24P. doi: https://doi.org/10.1042/cs068023Pb Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1985 The Biochemical Society and the Medical Research Society1985 Article PDF first page preview Close Modal You do not currently have access to this content.
