Roshan Siva

Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial

Evidence suggests that eosinophilic airway inflammation is important in the pathogenesis of severe chronic obstructive pulmonary disease (COPD) exacerbations. The present authors tested the hypothesis that a management strategy that aims to reduce sputum eosinophil counts is associated with a reduction in exacerbations of COPD. A total of 82 patients with COPD were randomised into two groups. One group was treated according to traditional guidelines (British Thoracic Society (BTS) group) and the other (sputum group) was treated with the additional aim of minimising eosinophilic airway inflammation, assessed using the induced sputum eosinophil count. The primary outcome was exacerbations, which were categorised as mild, moderate or severe. The frequency of severe exacerbations per patient per year was 0.5 and 0.2 in the BTS and sputum groups, respectively (mean reduction 62%). The majority of this benefit was confined to patients with eosinophilic airway inflammation. There was no difference in the frequency of mild and moderate exacerbations. The average daily dose of inhaled or oral corticosteroids during the trial did not differ between the groups. Out of 42 patients in the sputum group, 17 required regular oral corticosteroids to minimise eosinophilic airway inflammation. A management strategy that aims to minimise eosinophilic airway inflammation, as well as symptoms, is associated with a reduction in severe exacerbations of chronic obstructive pulmonary disease.

Sputum eosinophilia and the short term response to inhaled mometasone in chronic obstructive pulmonary disease

Background: An association between the sputum eosinophil count and the response to a 2 week course of prednisolone has previously been reported in patients with chronic obstructive pulmonary disease (COPD). Whether the response to inhaled corticosteroids is related to the presence of eosinophilic inflammation is unclear. Methods: A randomised, double blind, crossover trial of placebo and mometasone furoate (800 μg/day), each given for 6 weeks with a 4 week washout period, was performed in subjects with COPD treated with bronchodilator therapy only. Spirometric tests, symptom scores, chronic respiratory disease questionnaire (CRQ), and induced sputum were performed before and after each treatment phase. Results: Ninety five patients were recruited of which 60 were randomised. Overall there were no treatment associated changes in forced expiratory volume in 1 second (FEV1), total CRQ, or sputum characteristics. After stratification into tertiles by baseline eosinophil count, the net improvement in post-bronchodilator FEV1 increased with mometasone compared with placebo progressively from the least to the most eosinophilic tertile. The mean change in post-bronchodilator FEV1 with mometasone compared with placebo in the highest tertile was 0.11 l (95% CI 0.03 to 0.19). This improvement was not associated with a fall in the sputum eosinophil count. Conclusions: An increased sputum eosinophil count is related to an improvement in post-bronchodilator FEV1 following treatment with inhaled mometasone in COPD, but the improvement is not associated with a reduction in the sputum eosinophil count.

Multi-dimensional phenotyping: towards a new taxonomy for airway disease

All the real knowledge which we possess, depends on methods by which we distinguish the similar from the dissimilar. The greater the number of natural distinctions this method comprehends the clearer becomes our idea of things. The more numerous the objects which employ our attention the more difficult it becomes to form such a method and the more necessary. [ 1 ].

Peptic ulceration, Helicobacter pylori seropositivity and chronic obstructive pulmonary disease

We have suggested that chronic inflammation of other foregut derivatives might be associated with airway inflammation and amplification of the response to inhaled stimuli such as cigarette smoke leading to chronic obstructive pulmonary disease (COPD). One of the commonest causes of chronic foregut inflammation is gastritis secondary to Helicobacter Pylori infection. We tested the hypothesis that peptic ulceration and H. Pylori seropositivity are associated with COPD independently of other shared risk factors.

Effect of levofloxacin on neutrophilic airway inflammation in stable COPD: a randomized, double-blind, placebo-controlled trial

Rationale Airway inflammation persists after smoking cessation in established chronic obstructive pulmonary disease (COPD), suggesting that other factors drive the airway inflammatory response. Objectives We tested the hypothesis that high levels of bacterial colonization are associated with increased levels of neutrophilic airway inflammation in stable COPD by examining the cross-sectional relationship between these measurements and by conducting a randomized, double-blind, placebo-controlled study of the effect of levofloxacin in patients with stable COPD. Methods Patients were randomized to receive either levofloxacin 500 mg daily or placebo for 7 days and underwent sputum induction for a differential cell count and quantitative bacterial analysis at baseline and at days 7, 14, and 28. Results Sputum percentage neutrophil count correlated with airway bacterial load at baseline (r=0.56; P=0.003). Levofloxacin reduced bacterial load compared with placebo by 4.9-fold (95% confidence interval, 1.4–25.7; P=0.02) at day 7 but had no effect at any point on any marker of neutrophilic airway inflammation. In patients with a baseline bacterial load of more than 106 cfu/mL, levofloxacin treatment was associated with a 26.5% (95% confidence interval, 1.8%–51.3%; P=0.04) greater reduction in the percentage neutrophil count compared with placebo at day 7. Change in percentage neutrophil count correlated significantly with baseline airway bacterial load and change in airway bacterial load. Conclusion In stable COPD, levofloxacin treatment causes a short-term reduction in bacterial load. This is associated with a reduction in neutrophilic airway inflammation in patients with high bacterial loads. Further studies are required to investigate whether this effect is clinically advantageous.

COPD care delivery pathways in five European Union countries: mapping and health care professionals’ perceptions

Background COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services. Objective The aim of this study was to compare COPD patients’ care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals’ (HCPs) perceptions about the current pathways. Methods HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview. Results Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers. Conclusion Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients’ engagement could optimize current care pathways resulting in a better integrated system.

COPD: an inhaled corticosteroid-resistant, oral corticosteroid-responsive condition

To the Editors: Few areas of respiratory medicine have generated as much controversy as the use and purpose of long-term corticosteroid treatment in chronic obstructive pulmonary disease (COPD). However, several recent large, placebo-controlled studies have clarified the role of long-term treatment with inhaled corticosteroids 1–3. There is now consistent evidence that inhaled corticosteroid treatment, even in high doses, is not associated with a clinically significant reduction in the rate of decline of forced expiratory volume in one second (FEV1). Treatment is associated with a modest reduction in the frequency of more severe exacerbations, particularly in patients with more severe disease 1, 4 and in those who have a good bronchodilator response to short-term treatment with oral prednisolone 5, 6. The limited effects seen with inhaled corticosteroids is surprising, given that induced sputum evidence of corticosteroid-responsive eosinophilic airway inflammation is present in up to 40% of patients with stable moderate and severe COPD disease 7–10, …

User profiling for coordinated and integrated care

Integrated care has been increasingly advocated as an approach to promote better coordination of services and quality of care at different levels. In this study, views were elicited from different users of the healthcare system (patients, informal carers and healthcare professionals) in four European countries. The views pertained to current states of care and the role that remote patient monitoring and telehealth in general can play to facilitate effective implementation of integrated care. Overall, services were perceived to be fragmented at different levels ranging from personal to system fragmentation. Approaches such as telehealth, remote patient monitoring and having specialised urgent clinics in primary care were positively perceived by users as possible solutions for tackling fragmented care and for promoting better integration of services1.

Co-Morbidities as Predictors of Airflow Limitation among Smokers in England

The prevalence of co-morbidities among patients with Chronic Obstructive Pulmonary Disease (COPD) is well documented in the literature. Therefore, this pilot study aimed to identify whether co-morbidities screening would enhance COPD case-finding. Smoking patients were approached at Croydon University Hospital and two local community pharmacies (CPs). Their co-morbidities, respiratory symptoms, smoking pack-years and exercise capacity were collected. Airflow limitation was determined using handheld spirometry (COPD-6) device. The prevalence of airflow limitation was 42% (n = 21/50). The main identified predictors of airflow limitation were: co-morbidities (OR = 9, CI: 1.04–77.81, p = 0.025), respiratory symptoms (OR = 33.54, CI: 1.06–11.77, p = 0.039) and smoking history of ≥20 pack-years (OR = 3.94, CI: 1.13–13.64, p = 0.029). CPs were the main location for case-finding. This study demonstrated the need to screen for co-morbidities for COPD case-finding within CPs.

Experience of Using the WELCOME Remote Monitoring System on Patients with COPD and Comorbidities

The WELCOME system is an innovative telemonitoring system designed to provide constant monitoring of COPD patients also suffering from other major comorbidities. It consists of a sensors vest capable of recording various vital parameters in real time and transmitting them to the cloud via a tablet PC and wireless connection. In addition, peripheral devices record extra physiological data which is coupled with responses to validated health questionnaires that the patient responds to via the tablet. A dedicated medical decision support system (DSS) and a medical professional user interface support the system in providing automated detection of abnormal conditions. The obtained signals included Heart and Respiratory Rate, Body Posture, SpO2, multi-lead ECG, Auscultation and Electric Impedance Tomography. The system is tested with pilot studies in two European countries, Greece and UK. The preliminary results from the Greek pilot study are presented in this paper, highlighting the main findings from the first operational use of the WELCOME infrastructure.