Inhaled corticosteriod use and the risk of pneumonia and COPD exacerbations in the UPLIFT study

Rationale Unlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases. This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population. Objectives We aimed to determine rate and number of episodes of pneumonia and exacerbations of COPD in patients entering the study on no ICS, fluticasone proprionate (FP), and other ICS. Methods The UPLIFT dataset was examined retrospectively, and patients were divided into three groups based on their medications at entry: no ICS, FP and other ICS. Poisson regression was used to compare the frequency of respiratory adverse events. Measurements and main results At entry, the groups were well matched apart from a higher FEV1% predicted (38 vs. 41%; ICS vs. no ICS, respectively) and prevalence of current smoking (26 vs. 36%; ICS vs. no ICS, respectively). Incidence rates of pneumonia were significantly higher in patients taking ICS compared to no ICS (0.068 vs. 0.056 respectively; p = 0.012). When the FP group was compared to the other ICS, the event rate was even higher (0.077 vs. 0.058, respectively; p < 0.001). COPD exacerbations were more frequent in patients taking ICS, with significantly greater rate in the FP group compared to that seen with other ICS (0.93 vs. 0.84 respectively; p = 0.013). Conclusions ICS use was associated an increase in respiratory adverse event rates, but whether this was due to more severe illness at entry is unknown. In subgroup analysis, the excess of morbidity in the ICS group appeared to be mainly associated with those receiving FP at randomisation

Chronic cough hypersensitivity syndrome

Chronic cough has been suggested to be due to three conditions, asthma, post nasal drip, and reflux disease. A different paradigm has evolved in which cough is viewed as the primary condition characterised by afferent neuronal hypersensitivity and different aspects of this syndrome are manifest in the different phenotypes of cough. There are several advantages to viewing cough hypersensitivity as the unifying diagnosis; Communication with patients is aided, aetiology is not restricted and therapeutic avenues opened. Cough Hypersensitivity Syndrome is a more applicable label to embrace the clinical manifestations of this disabling disease. © 2013 Morice; licensee BioMed Central Ltd

Increased platelet reactivity in idiopathic pulmonary fibrosis is mediated by a plasma factor

Introduction Idiopathic Pulmonary Fibrosis (IPF) is a progressive, incurable fibrotic interstitial lung disease with a prognosis worse than many cancers. Its pathogenesis is poorly understood. Activated platelets can release pro-fibrotic mediators that have the potential to contribute to lung fibrosis. We determine platelet reactivity in subjects with IPF compared to age-matched controls. Methods Whole blood flow cytometry was used to measure platelet-monocyte aggregate formation, platelet P-selectin expression and platelet fibrinogen binding at basal levels and following stimulation with platelet agonists. A plasma swap approach was used to assess the effect of IPF plasma on control platelets. Results Subjects with IPF showed greater platelet reactivity than controls. Platelet P-selectin expression was significantly greater in IPF patients than controls following stimulation with 0.1 µM ADP (1.9% positive ±0.5 (mean ± SEM) versus 0.7%±0.1; p = 0.03), 1 µM ADP (9.8%±1.3 versus 3.3%±0.8; p<0.01) and 10 µM ADP (41.3%±4.2 versus 22.5%±2.6; p<0.01). Platelet fibrinogen binding was also increased, and platelet activation resulted in increased platelet-monocyte aggregate formation in IPF patients. Re-suspension of control platelets in plasma taken from subjects with IPF resulted in increased platelet activation compared to control plasma. Conclusions IPF patients exhibit increased platelet reactivity compared with controls. This hyperactivity may result from the plasma environment since control platelets exhibit increased activation when exposed to IPF plasma

Cough hypersensitivity syndrome: A few more steps forward

© The Korean Academy of Asthma, Allergy and Clinical Immunology. Cough reflex is a vital protective mechanism against aspiration, but when dysregulated, it can become hypersensitive. In fact, chronic cough is a significant medical problem with a high degree of morbidity. Recently, a unifying paradigm of cough hypersensitivity syndrome has been proposed. It represents a clinical entity in which chronic cough is a major presenting problem, regardless of the underlying condition. Although it remains a theoretical construct, emerging evidence suggests that aberrant neurophysiology is the common etiology of this syndrome. Recent success in randomized clinical trials using a P2X3 receptor antagonist is the first major advance in the therapeutics of cough in the past 30 years; it at last provides a strategy for treating intractable cough as well as an invaluable tool for dissecting the mechanism underpinning cough hypersensitivity. Additionally, several cough measurement tools have been validated for use and will help assess the clinical relevance of cough in various underlying conditions. Along with this paradigm shift, our understanding of cough mechanisms has improved during the past decades, allowing us to continue to take more steps forward in the future

Clinical history in gastroesophageal cough

SummaryGastroesophageal disease, a common cause of chronic cough, is often poorly recognised. We reviewed the presenting history of 47 chronic cough patients who had been proven to have gastroesophageal disease by oesophageal function testing. Fourty-seven patients (26 female), were enroled. Symptoms which were most common included: cough on phonation, on rising from bed, associated with certain foods or with eating in general. Symptoms known to be associated with laryngopharyngeal reflux, such as throat clearing, dysphonia, globus and dysphagia were also associated. Heartburn or indigestion was present in 63% of those questioned. These data show that symptoms associated with reflux in chronic coughers differ from those commonly perceived to be characteristic of classical heartburn-associated reflux. These data suggest that, contrary to previous reports, a symptom complex which is characteristic of reflux cough can be identified

The Cough Reflex: The Janus of Respiratory Medicine

In clinical practice, we commonly face adversity when encountering dysfunction of the cough reflex. Similar to ancient Roman deity Janus, it often presents with one of two opposing “faces”. Continual aberrant activation of the cough reflex, also known as chronic cough, can cause great detriment to quality of life and many of these patients are left misdiagnosed and undertreated. In contrast, loss of normal functioning of the cough reflex is the cause of a significant proportion of mortality in the elderly, primarily through the development of aspiration pneumonia. In this review we discuss both hyper- and hypo-activation of the cough reflex and how airway reflux and chronic aspiration may be involved in the aetiology and sequalae of both disease states. We detail the physiological and pharmacological mechanisms involved in cough, and how the recent development of P2X3 receptor antagonists may lead to the first pharmaceutical agent licensed for chronic cough. The treatment and prevention of loss of the cough reflex, which has been largely neglected, is also discussed as novel low-cost interventions could help prevent a number of hospital and domiciliary deaths from both acute and chronic aspiration

An audit of COPD: Diagnosis and management in general practice

Introduction: COPD is a spectrum of disorders primarily caused by smoking and characterised by progressive, not fully reversible airflow obstruction with a forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7. Methods: From November 2016 to March 2017 we audited patients with COPD in five general practices in Hull and East Riding, UK. We looked at deviation from the locally agreed guidelines. We extracted data on severity, exacerbations, medication and eosinophil count. Results: We assessed 1088 records. Median age was 70.9 years; 577 (53%) were male. About two-thirds of patients on the COPD register have an FEV1/FVC ratio in the diagnostic range for COPD, however, 388 (36%) out of 1088 had a ratio of ⩾0.7. In the patients with a ratio of ⩾0.7, 259 (67%) out of 388 had an FEV1 <80% of predicted. Patients with frequent exacerbations were more likely to be prescribed inhaled corticosteroid (ICS)-containing inhalers (incidence rate ratio of 2). FEV1 % predicted was a poor indicator of exacerbation frequency; however, the presence of elevated blood eosinophil counts (EOS) on at least two occasions was highly predictive of exacerbations. When ICSs, FEV1, EOS were examined in combination, they were highly significant predictors for exacerbations. Conclusion: FEV1 maybe a more accurate diagnostic parameter in primary care. Historical evidence of blood eosinophilia is a better predictor than FEV1. The combination of biomarkers may prove more accurate indicator of future exacerbation frequency, leading to targeted intervention