1,721,057 research outputs found

    Chronic cough: is the end nigh?

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    Chronic cough (lasting more than 8 weeks) is a common condition with substantial psychosocial impact. Despite huge efforts following robust guidelines, chronic cough in many patients remains refractory or unexplained (RU-CC). Recent insights support a significant role for cough hypersensitivity in RU-CC, including neuropathophysiological evidence from inhalational cough challenge testing, functional magnetic resonance imaging, and airway nerve biopsy. Along with improved approaches to measuring cough, this knowledge has developed in tandem with repurposing neuromodulator medications, including gabapentin, and evidence for non-pharmacological treatments. Most significantly, there is now a pipeline for novel classes of drugs specifically for chronic cough. The P2X3 receptor antagonist gefapixant is the first such drug to be approved in Europe. However, challenges persist. The field of chronic cough needs more robust epidemiological data, enhanced diagnostic tools, further well-designed clinical trials accounting for the effects of placebo, and treatments with minimal side-effects. Addressing these challenges are novel chronic cough registries, improved International Classification of Diseases (10th revision) coding, genetic testing options and further mechanistic studies. This Viewpoint article discusses these facets and considers how, whilst the end of chronic cough may not be imminent for all patients, the evolving landscape looks increasingly optimistic.Full Tex

    Measuring cough: what really matters?

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    The clinical and research discipline of cough has grown substantially over the last two decades as methods to measure cough have developed and evolved. Cough can be thought of both as a symptom and an objectively observable pathophysiological phenomenon, two aspects whose interrelationship is complicated. The following review explores the varied methods to measuring cough, both subjective, patient-reported measures and objective approaches. Specifically, symptom scores, questionnaires of cough-related quality of life, and associated mental health impacts of chronic cough are addressed, as are developments in measuring cough frequency, cough intensity, cough reflex sensitivity, and cough suppressibility. Measuring patient reported cough-severity with a simple visual analogue scale increasingly appears to be justified, but has limitations. The Leicester Cough Questionnaire has been widely used for twenty years, within varied settings and diseases, in research and routine clinical practice, and captures cough-related quality of life. Objective cough frequency has become the primary outcome measure for clinical trials of antitussives, and technology is now enabling the wider application of cough counting. Inhaled tussive challenge testing still has a role, including in the assessment of cough hypersensitivity, and in the identification of failure to supress cough. Ultimately, many measures have a contributory and complementary role, with differing merits in quantifying the multiple facets of cough, the complexity of which is being increasingly recognised.Full Tex

    Patient-reported assessments of chronic cough in clinical trials: accessory or primary endpoints?

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    Chronic cough is a complex disorder that affects up to 5-10% of the general population. It can be challenging to manage as there are few effective treatments, although several novel antitussives are in clinical development. The endpoints used to assess their efficacy in clinical trials should be optimal; most large clinical trials currently use objective measures as the primary outcome, especially cough frequency. There are strengths in this approach, although taking the view that other measures of chronic cough are less important, including patient-rated cough severity, psychosocial impact and other associated symptoms. Patient-reported outcome measures (PROMs) explore patients' personal experiences of health and disease, and the effects of particular conditions on their lives. Numerous validated PROMs exist for chronic cough, from simple visual analogue scales, to those that focus on cough hypersensitivity and cough-specific quality of life. Medicine regulators in the European Union (EU) and United States of America (USA) encourage the use of PROMs in clinical trials but have voiced concerns over their content validity, clinically meaningful thresholds for change, and discordance with objective measures. There are recent and ongoing studies to address these limitations. This review discusses currently available PROMs used to assess chronic cough and discusses their potential role as primary outcome measures in clinical trials.Full Tex

    Neurokinin-1 Receptor Inhibition and Cough

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    There is a need for better treatment for cough. Unexplained or chronic refractory cough (CRC) is the focus of several recent and ongoing large drug trials, with particular interest in antagonists of ATP-stimulated P2X receptors (1). Although such drugs appear very promising, there are nonresponders, and side effects may be unacceptable to some (2). Hence, a requirement for alternative approaches, not only for CRC but also for cough associated with chronic and incurable diseases of the lung, such as lung cancer, is needed. In this issue of the Journal, Smith and colleagues (pp. 737–745) present their findings on aprepitant for cough in non–radically treatable lung cancer, which, considering the current need, are very welcome (3).Full Tex

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Cough hypersensitivity and suppression in COPD

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    Cough reflex hypersensitivity and impaired cough suppression are features of chronic refractory cough (CRC). Little is known about cough suppression and cough reflex hypersensitivity in cough associated with chronic obstructive pulmonary disease (COPD). This study investigated the ability of patients with COPD to suppress cough during a cough challenge test in comparison to patients with CRC and healthy subjects. This study also investigated whether cough reflex hypersensitivity is associated with chronic cough in COPD. Participants with COPD (n=27) and CRC (n=11) and healthy subjects (n=13) underwent capsaicin challenge tests with and without attempts to self-suppress cough in a randomised order over two visits, 5 days apart. For patients with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured. Amongst patients with COPD, those with chronic cough (n=16) demonstrated heightened cough reflex sensitivity compared to those without chronic cough (n=11): geometric mean±sd capsaicin dose thresholds for five coughs (C5) 3.36±6.88 µmol·L−1 versus 44.50±5.90 µmol·L−1, respectively (p=0.003). Participants with CRC also had heightened cough reflex sensitivity compared to healthy participants: geometric mean±sd C5 3.86±5.13 µmol·L−1 versus 45.89±3.95 µmol·L−1, respectively (p<0.001). Participants with COPD were able to suppress capsaicin-evoked cough, regardless of the presence or absence of chronic cough: geometric mean±sd capsaicin dose thresholds for 5 coughs without self-suppression attempts (C5) and with (CS5) were 3.36±6.88 µmol·L−1 versus 12.80±8.33 µmol·L−1 (p<0.001) and 44.50±5.90 µmol·L−1 versus 183.2±6.37 µmol·L−1 (p=0.006), respectively. This was also the case for healthy participants (C5 versus CS5: 45.89±3.95 µmol·L−1 versus 254.40±3.78 µmol·L−1, p=0.033), but not those with CRC, who were unable to suppress capsaicin-evoked cough (C5 versus CS5: 3.86±5.13 µmol·L−1 versus 3.34±5.04 µmol·L−1, p=0.922). C5 and CS5 were associated with objective 24-h cough frequency in patients with COPD: ρ= −0.430, p=0.036 and ρ= −0.420, p=0.041, respectively. Patients with COPD-chronic cough and CRC both had heightened cough reflex sensitivity but only patients with CRC were unable to suppress capsaicin-evoked cough. This suggests differing mechanisms of cough between patients with COPD and CRC, and the need for disease-specific approaches to its management.No Full Tex

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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