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 in Musculoskeletal disorders: Using high resolution oesophageal manometry in search of an Aetiology

Chronic cough is a common symptom carrying significant morbidity which can occur as a result of oesophageal dysmotility. Here we report 2 patients with musculoskeletal disease presenting with chronic cough to our tertiary cough clinic. Prior to referral both patients had been extensively investigated to determine the basis of their cough, with no cause found. Oesophageal studies, using high resolution oesophageal manometry, demonstrated oesophageal dysmotility with consequent airway reflux. Anti-reflux therapy resulted in a good response in both patients. These are the first reports of the recently developed technique of high resolution manometry aiding the diagnosis of chronic cough. This technique may provide important clues into aetiological mechanism in patients with conditions predisposing to reflux into the airways. © 2012 Pathmanathan et al.; licensee BioMed Central Ltd

Effect of an electronic nicotine delivery device (e-Cigarette) on smoking reduction and cessation: a prospective 6-month pilot study

BACKGROUND: Cigarette smoking is a tough addiction to break. Therefore, improved approaches to smoking cessation are necessary. The electronic-cigarette (e-Cigarette), a battery-powered electronic nicotine delivery device (ENDD) resembling a cigarette, may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption. Efficacy and safety of these devices in long-term smoking cessation and/or smoking reduction studies have never been investigated. METHODS: In this prospective proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers (unwilling to quit) experimenting the 'Categoria' e-Cigarette with a focus on smoking reduction and smoking abstinence. Study participants were invited to attend a total of five study visits: at baseline, week-4, week-8, week-12 and week-24. Product use, number of cigarettes smoked, and exhaled carbon monoxide (eCO) levels were measured at each visit. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed. RESULTS: Sustained 50% reduction in the number of cig/day at week-24 was shown in 13/40(32.5%) participants; their median of 25 cigs/day decreasing to 6 cigs/day (p < 0.001). Sustained 80% reduction was shown in 5/40(12.5%) participants; their median of 30 cigs/day decreasing to 3 cigs/day (p = 0.043). Sustained smoking abstinence at week-24 was observed in 9/40(22.5%) participants, with 6/9 still using the e-Cigarette by the end of the study. Combined sustained 50% reduction and smoking abstinence was shown in 22/40 (55%) participants, with an overall 88% fall in cigs/day. Mouth (20.6%) and throat (32.4%) irritation, and dry cough (32.4%) were common, but diminished substantially by week-24. Overall, 2 to 3 cartridges/day were used throughout the study. Participants' perception and acceptance of the product was good. CONCLUSION: The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit (http://ClinicalTrials.gov number NCT01195597)

Clinicopharmacological profile of the fixed-dose combination of aclidinium bromide and formoterol fumarate in the management of chronic obstructive pulmonary disease

The recent Global Initiative for Chronic Obstructive Lung Disease (GOLD) chronic obstructive pulmonary disease (COPD) guidelines consider symptoms and exacerbation history in addition to the degree of airflow obstruction for classifying patients. The improvement of symptoms is principally provided by bronchodilators, using β 2 agonists and antimuscarinic agents. Aclidinium bromide is a novel long-acting antimuscarinic agent licensed for use in patients with COPD. Novel fixed-dose combinations that are either licensed or in their late phase of development include vilanterol/umeclidinium, indacaterol/glycopyrronium, olodaterol/tiotropium and formoterol/aclidinium. Fixed-dose combinations of aclidinium/formoterol have been evaluated in COPD patients and evidence suggests that this is efficacious, safe, has a quick onset of action and is well tolerated. This review provides a clinico-pharmacological profile of this compound

Dietary intervention in the treatment of patients with cough and symptoms suggestive of airways reflux as determined by Hull airways Reflux Questionnaire

Background: Chronic cough is a common and distressing symptom. Gastro-oesophageal reflux is a common cause of chronic cough however the symptom complex in cough is not confined to classic peptic symptoms. Dyspeptic symptoms have previously been shown to respond to dietary modifications and weight loss. We hypothesised that weight reduction maybe a useful non-pharmacological strategy in reducing reflux cough in the obese.Methods: Subjects with cough were recruited from Hull Cough Clinic. They were randomised to one of two open parallel groups; one receiving the traditional dietary modifications and the other weight reduction advice in the form of an Energy Prescription (EP). Cough symptoms, using the Leicester cough questionnaire (LCQ) and dietary intake were measured at the start and end of the study.Results: Thirty-three patients were recruited and 20 patients completed the study. Mean weight loss was 3.1 kg (p < 0.001) and reported an improvement in the LCQ (mean improvement 3.1); which is greater than the clinically significant score of 1.3. Moreover, secondary outcomes showed a significant association between baseline high calorie (r = -0.24; p < 0.001) and fat intake (r = -0.36; p = 0.001), and LCQ scores.Conclusion: A high calorie and fat intake is strongly correlated with cough score. Irrespective of diet, weight loss is associated with a reduction in cough symptoms. Asking patients to lose weight by reducing fat and calorie intake may be a simple strategy to ameliorate this intractable condition.Trial Registration: The study was approved by the local research ethics committee (South Humber Local Research Ethics Committee; REC04/Q1105/62). The study was registered with the Research and Development Department, Clinical Governance Directorate, Hull and East Yorkshire Hospitals NHS Trust (reference number R0086). © 2013 Smith et al.; licensee BioMed Central Ltd

Symptoms and exacerbations in asthma: an apparent paradox?

© The Author(s), 2019. Background: There is a dearth of data on prospectively recorded symptoms in patients with uncontrolled asthma. Asthma symptoms and exacerbation rate are commonly thought to be associated. The aim of this study was to analyse asthma symptoms of cough, wheeze, chest tightness and breathlessness in an uncontrolled asthma cohort. We also examined the effect of maintenance and reliever therapy (MART) on these symptoms and its effect on exacerbation rate. Methods: Adults with uncontrolled asthma electronically recorded their asthma symptom severity scores twice-daily over a period of 48 weeks following randomisation to beclometasone/formoterol twice daily plus pro re nata (prn) salbutamol or MART. Subjects with symptom scores of ⩾2 (ranging from 0 to 3 for each symptom) were considered more symptomatic, whereas those below a score of 2 were considered less severe. The influence treatment on exacerbation frequency and symptom profiles were then correlated. Results: Of the 1701 subjects in the analyses, 1403 were symptomatic with ⩾100 symptom episodes for one symptom. The remaining 298 subjects were classified as pauci-symptomatic. There was poor association between the frequency and symptom severity score for each symptom. Surprisingly, wheeze was the least reported symptom. Females were more likely to be polysymptomatic. MART compared with prn salbutamol markedly attenuated severe asthma exacerbations. This effect was most notable in subjects with fewer symptoms. Conclusions: In uncontrolled asthma, there is a poor correlation between reported symptoms and exacerbation frequency. This post hoc analysis suggests that MART should not be reserved for symptomatic subjects but achieves the greatest benefit in pauci-symptomatic patients with asthma. Trial registration: ClinicalTrials.gov identifier: NCT00861926

Asthma phenotypes: Do cough and wheeze predict exacerbations in persistent asthma?

Copyright © ERS 2017. Little is known of the long-term symptom profile in uncontrolled asthma and whether symptoms can predict distinct phenotypes. The primary objective of these analyses was to assess diurnal profile of cough and wheeze in an uncontrolled asthma population. Secondary outcomes were to examine how these symptom profiles influence response to treatment. Twice-daily electronically recorded data from 1701 patients were examined in relation to the population demographics. Reliever treatment with salbutamol was then compared with extra-fine beclometasone/formoterol maintenance and reliever therapy (MART). Exacerbation frequency was then correlated with the symptom profile. Symptoms were commoner in older patients with an increased body mass index. In most patients, reported cough and wheeze were closely correlated (r=0.73). Two phenotypes of cough- and wheezepredominant patients were identified; the former were overweight, older females and the latter older males. Diurnal symptoms of cough and wheeze were similarly attenuated by both therapies. MART reduced exacerbation frequency by a third compared with salbutamol, and this effect was greatest in patients with fewest reported symptoms. While cough and wheeze are highly correlated in uncontrolled asthma, some patients predominantly have cough whereas others wheeze. Symptoms and exacerbation frequency appear poorly associated, suggesting an alternative pathophysiology. MART may be the preferred option in those with fewest symptoms

Novel antitussive strategies

Acute and chronic cough represent one of the most common symptoms of medical importance but effective pharmacotherapy is, to all intents and purposes, absent. Numerous initiatives targeting the recently discovered tussive pathways are in progress. Here, we review the current antitussive armamentarium and provide an update on the novel strategies and compounds in development. © 2012 Elsevier Ltd