Alshafi, K

Boutou, AK

Hopkinson, NS

Polkey, MI

Raste, Y

Reid, J

English

PubMed

Spiral - Imperial College Digital Repository

2 Jakobsen M, Anker N, Dollerup J, et al. Study on drug costs associated with COPD prescription medicine inDenmark. Clin Respir J 2013; 7: 328–337.3 Blanchette CM, Dalal AA, Mapel D. Changes in COPD demographics and costs over 20 years. J Med Econ 2012; 15:1176–1182.4 Corsonello A, Pedone C, Corica F, et al. Polypharmacy in elderly patients at discharge from the acute care hospital.Ther Clin Risk Manag 2007; 3: 197–203.5 Hajjar ER, Hanlon JT, Artz MB, et al. Adverse drug reaction risk factors in older outpatients. Am J GeriatrPharmacother 2003; 1: 82–89.6 Gellad WF, Grenard JL, Marcum ZA. A systematic review of barriers to medication adherence in the elderly:looking beyond cost and regimen complexity. Am J Geriatr Pharmacother 2011; 9: 11–23.7 Hovstadius B, Åstrand B, Persson U, et al. Acquisition cost of dispensed drugs in individuals with multiplemedications – a register-based study in Sweden. Health Policy 2011; 101: 153–161.8 Almagro P, López Garcı́a F, Cabrera FJ, et al. Comorbidity and gender-related differences in patients hospitalizedfor COPD. The ECCO study. Respir Med 2010; 104: 253–259.9 Vestbo J, Hurd SS, Agustı́ AG, et al. Global strategy for the diagnosis, management, and prevention of chronicobstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 2013; 187: 347–365.10 Hajjar ER, Cafiero AC, Hanlon JT. Polypharmacy in elderly patients. Am J Geriatr Pharmacother 2007; 5: 345–351.11 Nobili A, Marengoni A, Tettamanti M, et al. Association between clusters of diseases and polypharmacy inhospitalized elderly patients: results from the REPOSI study. Eur J Intern Med 2011; 22: 597–602.12 Tinetti ME, Bogardus ST Jr, Agostini JV. Potential pitfalls of disease-specific guidelines for patients with multipleconditions. N Engl J Med 2004; 351: 2870–2874.13 Travers J, Marsh S, Caldwell B, et al. External validity of randomized controlled trials in COPD. Respir Med 2007;101: 1313–1320.14 Holmes HM. Rational prescribing for patients with a reduced life expectancy. Clin Pharmacol Ther 2009; 85:103–107.15 Cook DE, Sidel M, Belletti DA, et al. Review: clinical inertia in the management of chronic obstructive pulmonarydisease. COPD 2012; 9: 73–80.Eur Respir J 2014; 44: 791–794 | DOI: 10.1183/09031936.00014814 | Copyright ERS 2014Does a single Pseudomonas aeruginosaisolation predict COPD mortality?To the Editor:Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations(AECOPD) of their disease, which have a significant impact on their health status [1]. Evidence suggeststhat ,50% of these exacerbations are attributable to bacteria [2]. Pseudomonas aeruginosa can causeAECOPD and is associated with reduced survival in cystic fibrosis (CF) and bronchiectasis [3, 4]. Somestudies have found that the presence of P. aeruginosa is also associated with mortality in COPD, but thesefindings have been based on patients hospitalised with exacerbations [5, 6] or those hospitalised withmultidrug-resistant organisms [7].The impact of P. aeruginosa identified in sputum from COPD outpatients is less clear but is an importantissue for determining how aggressive strategies to attempt eradication should be. Therefore, we conducted anested case–control study to investigate whether the isolation of P. aeruginosa in the sputum of a generalCOPD population was associated with long-term mortality.We first identified all sputum specimen results from Royal Brompton Hospital (London, UK) microbiologyrecords between 2000 and 2012. These were cross-correlated with patients listed on our COPD researchaudit database. The reason for obtaining a sputum culture was not recorded systematically, but includedrepeated exacerbations and deterioration in symptom severity and/or clinical status, as well as opportunisticcollection from patients with chronic sputum production. The laboratory threshold for a culture to beconsidered P. aeruginosa positive was 200 CFU?mL-1 (a semi-quantitative method). For patients withrepeated positive sputum cultures the date of the first culture was recorded. Demographic variables, lungfunction measurements, gas transfer data, arterial blood gases and exacerbation frequency during the yearprior to entering the study were recorded for all patients.All analyses were performed using the Predictive Analytics Software (version 18; SPSS Inc., Chicago, IL,USA). Group comparisons were conducted utilising a t-test or the Chi-squared test as appropriate.Proportional Cox hazard analysis was utilised to assess: 1) the impact of parameters that differed betweenP. aeruginosa culture-positive and culture-negative groups and 2) the impact of antibiotic treatment onmortality. The proportionality hazard assumption was tested using partial residual plots (Schoenberg794residuals proportionality hazard test). The Kaplan–Meier survival curve with the Log rank comparison wasused to assess the impact of P. aeruginosa isolation on mortality and estimate the median survival of theP. aeruginosa culture-positive and culture-negative groups. A p-value ,0.05 was considered significant.The initial cohort consisted of 380 subjects (247 male and 133 female), with a mean¡SD age of66.3¡10.3 years and a forced expiratory volume in 1 s (FEV1) of 36.7¡18.3 % predicted. 95 (25%)patients from the initial population had at least one positive sputum culture for P. aeruginosa, while the resthad either negative cultures or cultured bacteria other than P. aeruginosa. 66 P. aeruginosa culture-positivepatients from the initial cohort were matched to another 66 P. aeruginosa culture-negative patients for sex,age and FEV1 % predicted.Differences in demographics and clinical characteristics between the initial COPD cohort and the studypopulation, and P. aeruginosa culture-positive and culture-negative patients are presented in table 1.Although the initial matching was done according to three baseline variables, the two final groups werefound to be similar in all recorded parameters of lung function (forced vital capacity, FEV1/forced vitalcapacity, diffusing capacity of the lung for carbon monoxide, transfer coefficient of the lung for carbonmonoxide, total lung capacity, residual volume and residual volume/total lung capacity), as well as bodymass index and arterial oxygen tension. Arterial carbon dioxide tension (p50.018) and exacerbation rate(p50.008) were higher in the P. aeruginosa culture-positive patients compared to the P. aeruginosa culture-negative patients (table 1). However, proportional Cox hazard analysis, which was conducted separately foreach group, indicated that exacerbation rate had no impact on mortality (P. aeruginosa culture-positive:hazard ratio 1.334 (95% CI 0.351–5.067), p50.672; P. aeruginosa culture-negative: hazard ratio 2.161 (95%CI 0.576–8.112), p50.253). The results were similar for arterial carbon dioxide tension (P. aeruginosa culture-positive: hazard ratio 1.134 (95% CI 0.758–1.697), p50.539; P. aeruginosa culture-negative: hazard ratio 1.074(95% CI 0.842–1.369), p50.572), indicating that it was not associated with survival.Median (range) survival for the study population (n5132) was 81.2 (50.8–109.5) months. During thisperiod 51 (38.6%) patients died, of these 52.9% (n527) were P. aeruginosa culture-positive and 47.1%(n524) were P. aeruginosa culture-negative. The Kaplan–Meier survival curve, using the Log rankcomparison, indicated that P. aeruginosa positive sputum culture was not associated with mortality inthis population. Median (range) survival for P. aeruginosa culture-positive patients was 80.1 (40.1–120.1)months compared to 88.6 (52–125.3) months in the P. aeruginosa culture-negative patients (p50.49)(fig. 1). Furthermore, no differences in survival as a function of the presence of Pseudomonas wouldhave been identified if the entire population of 380 had been analysed (data not shown).TABLE 1 Baseline differences between the initial cohort and the study population, and the Pseudomonas aeruginosa culture-positive and culture-negative groupsInitial cohort Study population p-value# P. aeruginosa culture-positive groupP. aeruginosa culture-negative groupp-value"Subjects n 380 132 66 66Age years 65.4¡10.9 68¡8.8 0.011 68¡8.8 68.3¡9 0.969Sex %Male 51.1 51.1 0.999Female 47.4 47.4BMI m?kg-2 24.7¡5.2 24¡6.3 0.257 23.6¡5.8 24.4¡6.8 0.497FEV1 % predicted 38.6¡20.1 (9–81.1) 33.6¡14.7 (12.6–72.4) 0.008 33.4¡14.5 (12.6–72.4) 33.8¡14.9 (12.9–71) 0.882FEV1/FVC % 40.6¡21.2 (13–69.8) 36.1¡16.8 (13.5–69.8) 0.029 35¡12.1 (14.1–69.8) 37.2¡20.7 (13.5–69.5) 0.456DLCO % predicted 43.7¡18.1 40.8¡17.4 0.157 41.5¡18.2 40.1¡16.7 0.663KCO % predicted 54.8¡21.6 54¡22.1 0.747 55.5¡21.8 52.5¡22.4 0.448TLC % predicted 123.7¡19.6 122.7¡17 0.662 121.1¡18.1 124.5¡15.6 0.286RV % predicted 205.1¡61.9 203.3¡53 0.780 206¡52.8 200.5¡53.6 0.569RV/TLC 155.2¡32.7 157¡32.1 0.639 60.3¡9.8 59.4¡11.6 0.647PaO2 kPa 9.5¡1.4 9.0¡1.5 0.014 9.1¡1.4 8.9¡1.8 0.440PaCO2 kPa 5.3¡0.8 5.5¡1.1 0.116 5.3¡0.9 5.8¡1.4 0.018Exacerbations per year 1.9¡0.7 2.1¡0.7 0.086 2.3¡0.7 1.9¡0.7 0.008Data are presented as mean¡SD or mean¡SD (range), unless otherwise stated. Bold signifies statistical significance. BMI: body mass index; FEV1:forced expiratory volume in 1 s; FVC: forced vital capacity; DLCO: diffusing capacity of the lung for carbon monoxide; KCO: transfer coefficient of thelung for carbon monoxide; TLC: total lung capacity; RV: residual volume; PaO2: arterial oxygen tension; PaCO2: arterial carbon dioxide tension.#: level of significance for comparison between the initial cohort and the study population; ": level of significance for comparison between the P.aeruginosa culture-positive and culture-negative groups.795A secondary analysis was also undertaken to identify whether Pseudomonas eradication treatment among P.aeruginosa culture-positive patients had any impact on survival. Sputum samples were ordered on a clinicalbasis and the decision of whether to attempt to eradicate Pseudomonas was at the discretion of the treatingphysician. Out of 66 P. aeruginosa culture-positive patients, 34 (25.8%) did not receive any treatment while32 (24.2%) were treated either with oral ciprofloxacin or appropriate intravenous antibiotics, dependingon resistance pattern. These two patient subgroups were similar regarding age, sex, body mass index,pulmonary function testing variables and exacerbation rate (data not shown). Cox proportional hazardanalysis indicated that P. aeruginosa treatment was not associated with mortality (hazard ratio 1.452 (95%CI 0.666–3.163), p50.348) among P. aeruginosa culture-positive patients.This study indicates that a single isolate of P. aeruginosa in sputum from a general COPD population isnot associated with worse survival. Recently, three different patterns of P. aeruginosa infection in COPDpatients have been described: 1) short carriage and clearance of a P. aeruginosa strain; 2) acquisition of anew strain associated with an AECOPD; and 3) persistence of P. aeruginosa colonisation with unknownclinical significance [8]. Although the specific pattern of P. aeruginosa infection was not investigated in thecurrent study, our results indicate that even though a single positive P. aeruginosa sputum culture wascorrelated with a higher exacerbation frequency, it was not associated with a worse long-term outcome inCOPD outpatients.The results of our study may, to some extent, be limited by its retrospective design and by the relativelysmall number of patients included, although a formal power estimation was not conducted. However, mostof the published studies in the field have used similar sample sizes to investigate the potential impact of P.aeruginosa infection on COPD survival [2, 6, 9]. Another limitation is the lack of baseline data on exercisecapacity, dyspnoea severity and frequency of previous hospitalisations, all of which could have affectedmortality. Moreover, high-resolution computed tomography of the chest was not systematically conductedin all patients so the prevalence of bronchiectasis, a factor which could have favoured P. aeruginosainfection, could not be estimated; although it should be noted that our institution runs separate clinics forpatients known to have either CF or non-CF bronchiectasis. However, several of these prognostic factors [6, 7]and imaging data [6, 7, 9] are also lacking in previously published studies that investigated the effect of P.aeruginosa on COPD mortality. Furthermore, careful patient matching has controlled for most of the lungfunction parameters that could affect mortality [10], so these negative results could not be attributed to aselected patient subgroup.In conclusion, this study indicated that a single P. aeruginosa sputum isolation is not a predictor of long-term mortality in a general COPD outpatient population. Current clinical practice usually targetsP. aeruginosa eradication using radical treatment, after its isolation in the sputum of a COPD patient withclinical deterioration or frequent exacerbations. Although eradicating Pseudomonas may be justified toimprove health status, patients and clinicians can, to an extent, be reassured by these data that if this is notpossible the impact on survival of a single P. aeruginosa isolation is not as significant as it is in CF [3] orbronchiectasis [4]. Future prospective, case–control studies are needed in order to define exact criteria forchronic P. aeruginosa infection in COPD patients and the best stratification criteria for a clinical trial ofP. aeruginosa eradication in COPD.0.80.60.40.21.0P. aeruginosa culture-negativeP. aeruginosa culture-positive0.01201008060Survival months40200 140Cumulative survivalFIGURE 1 Kaplan–Meier survivalcurve for the Pseudomonas aeruginosaculture-positive and P. aeruginosaculture-negative groups. p50.49 for P.aeruginosa culture-negative patients.796@ERSpublicationsA single positive Pseudomonas aeruginosa sputum culture is not associated with increased long-term mortality in COPD http://ow.ly/x5wvDAfroditi K. Boutou1, Yogini Raste1, Jeremy Reid1, Khalid Alshafi2, Michael I. Polkey1 and Nicholas S. Hopkinson11NIHR Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and ImperialCollege, London, UK. 2Dept of Microbiology, Royal Brompton Hospital, London, UK.Correspondence: Afroditi K. Boutou, 9–13, Stratigou Sarafi Str, Kalamaria, 55132 Thessaloniki, Greece.E-mail: afboutou@yahoo.comReceived: Dec 10 2013 | Accepted after revision: May 13 2014 | First published online: July 17 2014Support statement: This study was supported by the NIHR Respiratory Biomedical Research Unit (Royal Brompton andHarefield NHS Foundation Trust and Imperial College, London, UK).Conflict of interest: None declared.References1 Kelly JL, Bamsey O, Smith C, et al. Health status assessment in routine clinical practice: the chronic obstructivepulmonary disease assessment test score in outpatients. Respiration 2012; 84: 193–199.2 Wilson R, Sethi S, Anzueto A, et al. Antibiotics for treatment and prevention of exacerbations of chronicobstructive pulmonary disease. J Infect 2013; 67: 497–515.3 Pressler T, Bohmova C, Conway S, et al. Chronic Pseudomonas aeruginosa infection definition: EuroCareCFWorking Group report. J Cyst Fibros 2011; 10: Suppl. 2, S75–S78.4 Loebinger MR, Wells AU, Hansell DM, et al. Mortality in bronchiectasis: a long-term study assessing the factorsinfluencing survival. Eur Respir J 2009; 34: 843–849.5 Almagro P, Salvadó M, Garcia-Vidal C, et al. Pseudomonas aeruginosa and mortality after hospital admission forchronic obstructive pulmonary disease. Respiration 2012; 84: 36–43.6 Lin SH, Kuo PH, Hsueh PR, et al. Sputum bacteriology in hospitalized patients with acute exacerbation of chronicobstructive pulmonary disease in Taiwan with an emphasis on Klebsiella pneumoniae and Pseudomonas aeruginosa.Respirology 2007; 12: 81–87.7 Montero M, Domı́nguez M, Orozco-Levi M, et al. Mortality of COPD patients infected with multi-resistantPseudomonas aeruginosa: a case and control study. Infection 2009; 37: 16–19.8 Murphy TF. The many faces of Pseudomonas aeruginosa in chronic obstructive pulmonary disease. Clin Infect Dis2008; 1534–1535.9 Renom F, Yáñez A, Garau M, et al. Prognosis of COPD patients requiring frequent hospitalization: role of airwayinfection. Respir Med 2010; 104: 840–848.10 Boutou AK, Shrikrishna D, Tanner RJ, et al. Lung function indices for predicting mortality in COPD. Eur Respir J2013; 42: 616–625.Eur Respir J 2014; 44: 794–797 | DOI: 10.1183/09031936.00023414 | Copyright ERS 2014ERJ Open articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 3.0.Does traffic noise influence respiratorymortality?To the Editor:Over the last decade, several studies have investigated the association between noise levels, primarily due toroad traffic in large cities, and pathologies not related to either traditional hearing impairments or sleepdisorders. These pathologies are mainly hypertension and cardiovascular, connective system and respiratorydiseases [1]. Their impact on public health has been assessed in time series studies, indicating a traffic noiseeffect on both cardiovascular and respiratory hospital admissions rates similar to that attributed to airpollutants [2]. In addition, a recent study has shown an association of noise levels with cardiovascularmortality [3]. The description of the physiopathological mechanisms involved in this association reveal anactual impact of current road traffic noise levels on health [1]. Others question this because of the highcorrelation between traffic noise and air pollution [4], although a previous study in our setting showed anindependent association between noise and cardiovascular mortality from the effect of the primary chemicalair pollutants [5]. However, the effect of noise on respiratory mortality has not yet been investigated.In this study, we examined the association between daily mortality due to respiratory causes (InternationalClassification of Diseases, 9th revision, codes 460–519) and daytime noise levels in the city of Madrid797

Does a single Pseudomonas aeruginosa isolation predict COPD mortality?

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Does a single Pseudomonas aeruginosa isolation predict COPD mortality?

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