Efficacy and safety of AZD1981, a CRTH2 receptor antagonist, in patients with moderate to severe COPD

SummaryObjectiveTo evaluate the efficacy and tolerability of the selective CRTh2 (DP2) receptor antagonist AZD1981 compared with placebo in patients with moderate to severe COPD.MethodsIn this multicentre, randomised, double-blind, parallel-group, phase IIa study (ClinicalTrials.gov identifier: NCT00690482) patients with moderate to severe COPD received either AZD1981 1000 mg twice daily or matching placebo for 4 weeks. Inhaled terbutaline was used as-needed as reliever medication throughout. The co-primary endpoints were change from baseline to end of treatment in pre-bronchodilator forced expiratory volume in 1 s [FEV1] and the Clinical COPD Questionnaire (CCQ). Additional endpoints included other lung function measures, 6-min walk test (6-MWT), COPD symptom score, reliever medication use and tolerability.Results118 patients were randomised to treatment (AZD1981 n = 61; placebo n = 57); 83% of patients were male and the mean age was 63 years (range 43–83). There were no significant differences in the mean difference in change from baseline to end of treatment between AZD1981 and placebo for the co-primary endpoints of pre-bronchodilator FEV1 (AZD1981–placebo: −0.015, 95% CI: −0.10 to 0.070; p = 0.72) and CCQ total score (difference: 0.042, 95% CI: −0.21 to 0.30; p = 0.75). Similarly, no differences were observed between treatments for the other outcomes of lung function, COPD symptom score, 6-MWT, BODE index, and use of reliever medication. AZD1981 was well tolerated.ConclusionThere was no beneficial clinical effect of AZD1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD1981 was well tolerated and no safety concerns were identified

Long-term survival for COPD patients receiving noninvasive ventilation for acute respiratory failure

Implementation of noninvasive ventilation (NIV) as an add-on treatment has been routinely used in a non-intensive care setting since 2004 for patients with chronic obstructive pulmonary disease (COPD) and acute hypercapnic respiratory failure at a university hospital in Denmark. Although randomized controlled trials show lowered mortality rates in highly selected patients with acute exacerbation and respiratory failure, there are only few reports on long-term survival after receiving NIV. We present long-term all-cause mortality data from patients receiving NIV for the first time. METHOD: Data from medical records were retrospectively retrieved from all patients receiving NIV for the first time after being admitted acutely to an acute medical ward and further transfer to a respiratory ward with respiratory failure and a diagnosis of COPD in the period January 1, 2005 to December 31, 2007; patients were followed until January 2012. Demographic data collected included age, sex, diagnoses at discharge, and, when present, FEV(1); a “not-to-intubate” order was also registered when listed. RESULTS: In total, 253 patients (143 female, 110 male) received NIV for the first time. The median age was 72 years (range 46–91 years). The 30-day mortality rate was 29.3%. The 5-year survival rate was 23.7%. Women showed a trend towards better survival than men (25.7% vs 19.2%, P = 0.25), and the trend was even more pronounced for patients with COPD. CONCLUSION: The mortality rate of patients receiving NIV is high, as expected in a real-life setting, but with a 5-year survival rate of 23.7% with a trend towards more female than male long-term survivors

Observational studies assessing the pharmacological treatment of obstructive lung disease : strengths, challenges and considerations for study design

Acknowledgements: Editorial support under the direction of the authors was provided by Richard Knight, CMC Connect, McCann Health Medical Communications, and funded by AstraZeneca in accordance with Good Publication Practice guidelines. The first draft of the manuscript was written in three sections by J. Vestbo, C. Janson and D. Price. Editorial support specifically for D. Price was provided by Antony Hardjojo of the Observational and Pragmatic Research Institute, Singapore. J. Vestbo is supported by the NIHR Manchester BRC.Peer reviewedPublisher PD

Beta-blockers in COPD:time for reappraisal

Peer reviewedPostprin

Absence of <i>Pneumocystis jirovecii</i> colonization in human immunodeficiency virus-infected individuals with and without airway obstruction and with undetectable viral load

Pneumocystis jirovecii colonization has been associated with non-acquired immune deficiency syndrome (AIDS) pulmonary comorbidity. We used spirometry to measure pulmonary function and analyzed oral wash specimens by quantitative polymerase chain reaction (PCR), targeting the large mitochondrial ribosomal subunit. For sensitivity control, a blinded subsample was subjected to touch-down PCRs, targeting both large and small ribosomal subunits and the major surface glycoprotein. Pneumocystis jirovecii deoxyribonucleic acid (DNA) was detected in 1 of 156 (95% confidence interval, .1%–3.5%) virologically suppressed human immunodeficiency virus (HIV)-infected individuals confirmed by all PCR methods. Thus, prevalence of P jirovecii colonization was low and unlikely to be a major cause of pulmonary comorbidity in this group of well treated HIV-infected individuals

A systematic literature review of Patient Reported Outcome Measures (PROMs) used in the assessment and measurement of sleep disorders in Chronic Obstructive Pulmonary Disease

BACKGROUND: Sleep problems are common in patients with chronic obstructive pulmonary disease (COPD), but the validity of patient-reported outcome measures (PROMs) that measure sleep dysfunction has not been evaluated. We have reviewed the literature to identify disease-specific and non-disease-specific sleep PROMs that have been validated for use in COPD patients. The review also examined the psychometric properties of identified sleep outcome measures and extracted point and variability estimates of sleep instruments used in COPD studies. METHODS: The online EMBASE, MEDLINE, PsycINFO, and SCOPUS databases for all years to May 2014 were used to source articles for the review. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Criteria from the Medical Outcomes Trust Scientific Advisory Committee guidelines were used to evaluate the psychometric properties of all sleep PROMs identified. RESULTS: One COPD-specific and six non-COPD-specific sleep outcome measures were identified and 44 papers met the review selection criteria. We only identified one instrument, the COPD and Asthma Sleep Impact Scale, which was developed specifically for use in COPD populations. Ninety percent of the identified studies used one of two non-disease-specific sleep scales, ie, the Pittsburgh Sleep Quality Index and/or the Epworth Sleep Scale, although neither has been tested for reliability or validity in people with COPD. CONCLUSION: The results highlight a need for existing non-disease-specific instruments to be validated in COPD populations and also a need for new disease-specific measures to assess the impact of sleep problems in COPD

Prevalence of airflow obstruction in patients with stable systolic heart failure

Abstract Background Chronic obstructive pulmonary disease (COPD) is an important differential diagnosis in heart failure (HF). However, routine use of spirometry in outpatient HF clinics is not implemented. The aim of the present study was to determine the prevalence of both airflow obstruction and non obstructive lung function impairment in patients with HF and to examine the effect of optimal medical treatment for HF on lung function parameters. Methods Consecutive patients with HF (ejection fraction (EF)\u2009<\u200945%) and New York Heart Association (NYHA) functional class II-IV at 10 different outpatient heart failure clinics were examined with spirometry at their first visit and after optimal medical treatment for HF was achieved. airflow obstruction was classified and graded according to the GOLD 2011 revision. Results Baseline spirometry was performed in 593 included patients and 71 (12%) had a clinical diagnosis of COPD. Mean age was 69\u2009\ub1\u200911\ua0years and mean EF was 30\u2009\ub1\u20099%. Thirty-two % of the patients were active smokers and 53% were previous smokers. Mean FEV 1 and FVC was 77.9\u2009\ub1\u20091.7% and 85.4\u2009\ub1\u20091.5% of predicted respectively. Obstructive pattern was observed in 233 (39%) of the patients. Of these, 53 patients (9%) had mild disease (GOLD I) and 180 (30%) patients had moderate to very severe disease (GOLD II-IV). No difference in spirometric variables was observed following up titration of medication. Conclusion In stable patients with HF airflow obstruction is frequent and severely underdiagnosed. Spirometry should be considered in all patients with HF in order to improve diagnosis and treatment for concomitant pulmonary disease

Depression and its relationship with poor exercise capacity, BODE index and muscle wasting in COPD

SummaryBackgroundThe prevalence of depression in stable COPD patients varies markedly, possibly because of use of different scales. We aimed to assess depression using 2 different depression scales and to examine the association between depression and poor exercise performance, BODE index and muscle wasting in clinically stable COPD patients.Methods122 stable COPD patients were assessed with the Centre for Epidemiologic Studies Depression Scale (CES-D) and the Brief Assessment Schedule Depression Cards (BASDEC). We also assessed patients with spirometry, bioelectrical impedance analysis, 6-minute walk distance (6MWD), St George's Respiratory Questionnaire (SGRQ) and MRC dyspnoea and Borg scales.ResultsThe CES-D and BASDEC scales detected almost similar prevalence rates of depression (21% vs 17%) with a Kappa coefficient of 0.68, p<0.0001. The BASDEC scale detected more depression in women and was more closely associated with dyspnoea than the CES-D. COPD severity was associated with depression when using BODE scores but not when GOLD categories were used. Each of the CES-D and BASDEC depression scores were associated with 6MWD after adjusting for FEV1% predicted, gender, age and pack-years (p=<0.0001 and 0.001, respectively). Also, patients with a 6MWD<350 scored significantly higher on both depression scales. Wasted patients appeared to have higher depression scores, but the difference was statistically insignificant.ConclusionThe administration of different depression scales may affect some of the characteristics of depressed patients rather than the prevalence rate of depression. Depression was associated with poor exercise performance and BODE index in COPD

The global impact of Aspergillus infection on COPD

From Springer Nature via Jisc Publications RouterHistory: received 2020-07-15, registration 2020-08-05, accepted 2020-08-05, pub-electronic 2020-09-11, online 2020-09-11, collection 2020-12Publication status: PublishedFunder: Manchester Biomedical Research Centre; doi: http://dx.doi.org/10.13039/100014653Abstract: Background: Advanced chronic obstructive pulmonary disease (COPD) often leads to hospitalisation and invasive aspergillosis (IA) is a serious complication. Aspergillus sensitisation may worsen symptoms in COPD. Methods: We identified published papers between January 2000 and May 2019 with > 50 subjects and GOLD criteria for grade II, III or IV (FEV1/FVC 0.05). Conclusions: The prevalence of COPD is much higher than previously estimated. Overall COPD mortality may be higher than estimated and IA probably contributes to many deaths. Improved rapid diagnosis of IA using culture and non-culture based techniques is required in COPD hospital admissions to reduce mortality