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EDITORIALS

We are delighted to announce that the Primary Care RespiratoryJournal (PCRJ) will be published by Nature Publishing Group(NPG) from 1st April this year. NPG have entered into apartnership agreement with the Primary Care Respiratory SocietyUK (PCRS-UK), the owners of the Journal, to re-launch the PCRJunder a new title brand. The rebranded PCRJ will continue as theofficial journal of the PCRS-UK and the International Primary CareRespiratory Group (IPCRG). PCRS-UK has worked in closecollaboration with the IPCRG, as well as the editorial team, whilstnegotiating the partnership agreement.

This partnership with NPG means that the journal will nowbenefit hugely from the strengths and capabilities of a topinternational academic publisher. There will be a change in title,to include the words ‘respiratory medicine’. This is aimed atbroadening the relevance of the journal to practitioners workingin a range of international models of primary care, making it clearthat we are interested in receiving contributions from cliniciansand academics working within any sector that impacts on primarycare management of respiratory and respiratory-related allergicdiseases. The publishing partnership with NPG will be officiallylaunched at the IPCRG conference in Athens, 21–24 May 2014.

This issue of the PCRJ will therefore be the final issue of thejournal in its current form, and will be the last to have a hard copyissue. The rebranded journal will be online-only and fully open-access, with an article processing charge (APC). This new businessmodel for the journal will ensure sustainable access to all of ourpublished content free of charge to readers anywhere in theworld. This will help ensure longevity and sustainability in anenvironment of constant change, where funding agencies aremore and more mandating publication of research in open-accessjournals.

The aim, of course, is to continue the progress made by the

PCRJ in recent years and to develop the journal into a worldleader in its field. We obtained our first Impact factor of 2.191last year, which ranked the PCRJ as 2/17 among primary carejournals and 30/50 among respiratory journals. Our internalcalculations predict that our 2013 Impact factor, to be publishedin June 2014, will be above 2.5. NPG has the experience,expertise, worldwide reputation, global reach and infrastructurethat the journal needs to develop further. The tendering,negotiating and planning process we have been through withNPG gives us every confidence that this is going to be a verysuccessful partnership which will help to improve the quality ofthe end-product and increase its global reach. As such, we arevery excited at the prospect of working with such an illustriouspublisher.

There will be a seamless transfer from the current PCRJpublishing arrangements to the new publishing arrangementswith NPG. Any articles submitted to the PCRJ up to the end ofMarch 2014 will be automatically transferred over to the newtitle. Articles submitted to the journal from 1st April 2014 will besubject to the APC. We fully understand that the introduction ofan APC, payable on article acceptance, is a new venture for thisjournal. Of course, authors from HINARI-band countries will havetheir APC waived, and other authors who cannot afford to payand/or do not have a source of funding, can apply for a waiver ifabsolutely necessary. However, we hope that the Nature brand,the PCRJ’s reputation and well-established editorial processes,and our fast turnaround for submitted papers, should be veryattractive to authors who wish to submit their work. In 2013, theaverage time to first decision for submitted papers was 23.7 days,and the time to final decision was 30.7 days.

Making the move to a new publisher is a major decision forany journal owner. Having worked very closely with the PCRS-UKwe are well aware that considerable thought, expertise andnegotiation has gone into this decision, which has beenmotivated by one core aim – ensuring that the journal continuesto shape efforts to develop primary care respiratory medicineglobally. It has been our pleasure to have been part of thesedeliberations and to work alongside a number of talented andhighly committed individuals who have brought this agreementto fruition. They include: Anne Smith and Patrick White(representing the PCRS-UK); Siân Williams (representing theIPCRG); Mark Ware (an independent editorial consultant); PoojaAggarwal and Joe Bennett (of NPG), and Richard Smith, Dermot

Exciting times ahead: a partnership with NaturePublishing Group

Paul Stephenson, Aziz Sheikh

Editors-in-Chief, Primary Care Respiratory Journal

*Correspondence: c/o PCRJ Editorial Office, Unit 2, WarwickHouse, Fairview Industrial Estate, Kingsbury Road, Curdworth,Sutton Coldfield, B76 9EE, UKTel: +44 (0)1675 475401 Fax: +44 (0)121 336 1914E-mail: tricia@pcrs-uk.org

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Autoimmunity has been defined as a T-helper cell type 1 (Th/1)immune phenomenon, which creates an inflammatory responsein the body against normal body substances (tissues/proteins).Allergy on the other hand is a T-helper cell type 2 (Th/2) immuneresponse to foreign antigen that also leads to inflammation.Because these two classes of immune disorders involve differentclusters of differentiation 4 (CD4+) T-helper cell subsets, hithertothey have been considered immunologically separate and distinct– i.e. not caused by the same underlying genetic andenvironmental factors. However, in this issue of the PCRJ, Maasand colleagues have studied the co-occurrence of these immunediseases in families in the general population of the Netherlands,and have found that a diagnosed autoimmune disease in theparents suggested a roughly 2-fold increased risk of allergicdisease in the eldest child.1 Their data suggest that there may bemore of a common aetiology for these two types of immunedisorders than previously thought.2,3

Critical to the interpretation of the paper by Maas et al. is the issueof disease classification. The investigators used the InternationalClassification of Primary Care (ICPC) diagnoses to define autoimmunedisease in the parents. This system identifies the seven most common

autoimmune diseases: psoriasis, rheumatoid arthritis/ankylosingspondylitis, ulcerative colitis/Crohn’s disease, diabetes mellitus type 1,and multiple sclerosis. There are many more autoimmune diseasesthat were excluded from consideration because they are rare andhence not included in the ICPC. Including these rarer disorders mighthave made the results of the study even stronger. The allergic diseasesclassified included allergic asthma, hay fever, atopic dermatitis, andatopic conjunctivitis. This disease classification was relatively completeand thus misclassification bias is unlikely to have occurred for thisoutcome. Another methodological concern is that non-paternity wasassessed and judged to be at an acceptable level; again, morestringent criteria for non-paternity would only have strengthened theresults.

As noted by the authors,1 epidemiological data suggesting familialaggregation of these types of immune disorders in families isconflicting, and for some studies, statistical power has been limited bythe low prevalence of the autoimmune diseases. Again, as noted bythe authors, small sample size was an issue in some of the priorstudies, as well as incomplete ascertainment of autoimmunedisease.4,5 In contrast to the autoimmune diseases, the prevalence ofallergy is high, and thus familial aggregation can occur simply by highdisease prevalence alone.

The central question is whether this disease co-occurrence is justdue to the nonspecific “environmental and epigenetic and geneticeffects” alluded to by Maas and colleagues,1 or is there a hypothesisthat might explain the underlying co-occurrence of autoimmune andallergic diseases in families?

I think there is a hypothesis as to what has caused a rise inprevalence of both Th1- and Th2-mediated immune diseases. First,the rise in both Th2 and Th1 immune diseases suggests that theimmunological defect is at the next level up from the CD4 +, Th1, andTh2 cell, namely at the level of the T-regulatory cell (T-reg); these cellscontrol both Th2 and Th1 inflammatory responses. These T-reg cellsare in turn under the control of vitamin D, corticosteroids, and thecellular cytokines Transforming Growth factor Beta one (TGFB1) and

Vitamin D and the HLA locus help to explain the relationshipbetween autoimmune and allergic diseases

*Scott T Weiss1

1 Professor of Medicine, Harvard Medical School; Associate Director, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston MA, USA

*Correspondence: Professor Scott T Weiss, Professor ofMedicine, Harvard Medical School, Department of Medicine,Brigham and Women's Hospital, Boston MA 02115, USATel: +617 525 2278 Fax: +617 525 4488E-mail: scott.weiss@channing.harvard.edu

See linked article by Mass et al. on pg 14

Ryan, John Haughney and Wisia Wedzicha (who provided veryhelpful strategic advice).

As ever, we are extremely grateful to our superb team ofassistant, statistical, section and associate editors, as well as thePCRS-UK and IPCRG representatives and everyone on the PCRJInternational Editorial Board, for their support and guidance. Wemust also thank everyone who has contributed their time andexpertise to review manuscripts for the PCRJ in 2013; this work,undertaken despite very busy schedules by experts in their field,is fundamental to our success in publishing high quality peer-reviewed articles, and we are enormously grateful. The list ofPCRJ 2013 reviewers is available online at www.thepcrj.org as anappendix to this editorial.

Finally, we would like to record our debt of gratitude to theteam in the PCRJ editorial office, who have provided us with suchstalwart support over many years. Led by Tricia Bryant and ablysupported by Gail Ryan, Helen McDonnell, Liz Stockman, andLynn Danzig, they have been the backbone of the journal. Thesuccess of the PCRJ and its continued development is in no smallpart a tribute to their dedication and hard work.

Conflicts of interest The authors declare that they have no conflicts ofinterest in relation to this article.

Online 28th February 2014© 2014 Primary Care Respiratory Society UK. All rights reservedhttp://dx.doi.org/10.4104/pcrj.2014.00022Prim Care Respir J 2014; 23(1): 1-2

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interleukin 10 (IL10). Higher levels of vitamin D lead to up-regulationof IL10 and TGFB1, the subsequent up-regulation of effector T-regulatory cell activity, and the down-regulation of inflammation (bothTh1 or Th2).6 In addition, higher levels of vitamin D lead to decreaseddendritic cell signaling to the T-regulatory cells, which means adecreased antigenic input to these controller cells.6 Finally, vitamin Dlevels are important epigenetic activators that establish signallingbetween mother and fetus and induce downstream gene expressionin over 5000 genes when comparing the sufficient and the deficientstates of the mother.7

There are several features that are attractive about this theory.First, it provides a plausible set of environmental factors – e.g. sunexposure, cod liver oil intake, and subsequent vitamin D levels – toexplain the epidemiology of a rise in both Th1 and Th2 disease overthe past 50 years, a time when vitamin D levels in the population havebeen decreasing. The causes of the epidemic of vitamin D deficiencyand its role in fetal development and disease have been welldocumented.6,8-12

However, whilst I believe that vitamin D is responsible for much ofthe fetal origins of disease, vitamin D deficiency alone cannot accountfor the wide variation in clinical disease phenotypes seen for bothautoimmunity and allergy. As noted by Maas et al.,1 there must alsobe a genetic component. I believe that the primary common geneticcomponent is the HLA locus located on chromosome 6. For both theallergic and the autoimmune diseases there are specific HLA genesthat are associated with disease occurrence. Indeed, it is thecombination of specific HLA genes and low vitamin D that results ineach of the specific autoimmune and allergic diseases. Whether it isHLAB27 for ankylosing spondylitis or HLADRB1 for allergic asthma,the HLA alleles confer disease phenotype specificity in the setting oflow vitamin D. This concept of a vitamin D-HLA interaction is not noveland is well established in the published literature; a Pub Med searchidentifies 239 articles on the relationship between vitamin D and HLA,including articles on all seven of the Th1 autoimmune diseases of theMaas study, and asthma. Are there other genes involved besides HLA?Almost certainly, there are. Further genomic studies in the relevanttissues will yield the networks of additional genes involved. However,it is specifically HLA interacting with vitamin D that gives thesedisorders a common pathophysiology.

Given this hypothesis there is one essential question: what can bedone to prove that low vitamin D and HLA are the primaryenvironmental and genomic drivers for the co-occurrence of thesedisorders? We need to do large randomised controlled trials of vitaminD supplementation to pregnant women at high risk of allergy orautoimmune disease where genomics are measured and the co-occurrence of allergies and autoimmune disease are also measured.The limiting factor will be the incidence of the autoimmune diseases.However, type-one diabetes is relatively common, and if coupled with

multiple other autoimmune disease outcomes with sufficiently longfollow-up, such a trial is feasible. Obviously, measurement of HLA inboth parents and offspring in such a trial will be critical as well. WhileHLA genotype can’t be changed, vitamin D deficiency can be lookedfor and addressed. This then represents an important possibility forintervention and prevention of all of these disorders.

Conflicts of interest The author is supported by NIH grants including a grantto study the effect of vitamin D supplementation in pregnant women andprevention of asthma in their offspring: U01 HL091528.

Commissioned article; not externally peer reviewed; accepted 13th January 2014;online 19th February 2014© 2014 Primary Care Respiratory Society UK. All rights reservedhttp://dx.doi.org/10.4104/pcrj.2014.00009Prim Care Respir J 2014; 23(1): 2-3

References 1. Maas T, Nieuwhof C, Passos VL, et al. Transgenerational occurrence of allergic

disease and autoimmunity: general practice-based epidemiological research. Prim

Care Respir J 2014;23(1):14-21. http://dx.doi.org/10.4104/pcrj.2013.00108

2. Simpson CR, Anderson WJ, Helms PJ, et al. Coincidence of immune-mediated

diseases driven by Th1 and Th2 subsets suggests a common aetiology. A

population-based study using computerized general practice data. Clin Exp Allergy.

2002;32(1):37-42. http://dx.doi.org/10.1046/j.0022-0477.2001.01250.x

3. Sheikh A, Smeeth L, Hubbard R. There is no evidence of an inverse relationship

between TH2-mediated atopy and TH1-mediated autoimmune disorders: Lack of

support for the hygiene hypothesis. J Allergy Clin Immunol 2003;111(1):131-5.

http://dx.doi.org/10.1067/mai.2003.8

4. Rudwaleit M, Andermann B, Alten R, et al. Atopic disorders in ankylosing

spondylitis and rheumatoid arthritis. Ann Rheum Dis 2002;61:968-74.

http://dx.doi.org/10.1136/ard.61.11.968

5. EURODIAB. Decreased prevalence of atopic diseases in children with diabetes.

TheEURODIAB Substudy 2 Study Group. J Pediatr 2000;137:470-4.

http://dx.doi.org/10.1067/mpd.2000.109109

6. Litonjua AA, Weiss ST. Is vitamin D deficiency to blame for the asthma epidemic? J

Allergy Clin Immunol 2007;120(5):1031-5.

http://dx.doi.org/10.1016/j.jaci.2007.08.028

7. Bossé Y, Lemire M, Poon AH, et al. Asthma and genes encoding components of the

vitamin D pathway. Respir Res 2009;10:98.

http://dx.doi.org/10.1186/1465-9921-10-98

8. Weiss ST, Litonjua AA. Maternal diet vs lack of exposure to sunlight as the cause of

the epidemic of asthma, allergies and other autoimmune diseases. Thorax

2007;62(9):746-8. http://dx.doi.org/10.1136/thx.2007.079707

9. Weiss ST, Litonjua AA. Childhood asthma is a fat-soluble vitamin deficiency disease.

Clin Exp Allergy 2008;38(3):385-7.

http://dx.doi.org/10.1111/j.1365-2222.2007.02920.x

10. Weiss ST. Asthma in early life: is the hygiene hypothesis correct? J Pediatr (Rio J)

2008;84(6):475-6. http://dx.doi.org/10.2223/JPED.1857

11. Weiss ST, Litonjua AA. The in utero effects of maternal vitamin D deficiency: how

it results in asthma and other chronic diseases. Am J Respir Crit Care Med

2011;183(10):1286-7. http://dx.doi.org/10.1164/rccm.201101-0160ED

12. Weiss ST. Bacterial components plus vitamin D: the ultimate solution to the asthma

(autoimmune disease) epidemic? J Allergy Clin Immunol 2011;127(5):1128-30.

http://dx.doi.org/10.1016/j.jaci.2011.02.025

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The importance of comorbidity in patients with asthma is amplydemonstrated in the study by Steppuhn and colleagues in thisissue of the PCRJ.1 In an analysis of a large population sample ofadults with asthma in Germany they found high levels ofcomorbidity of other important chronic conditions. Indeed, adultswho only had asthma were in a minority, with over 60% ofasthma sufferers having one or more additional comorbidities outof a list of eight conditions (diabetes mellitus, hypertension,chronic heart failure, depression, osteoarthritis, stroke, coronaryheart disease, and cancer). For seven of these eight conditions(cancer being the exception), prevalence rates were higher inpatients with asthma compared with the general population,even after adjusting for potential confounding variables. Themajority of patients with comorbidity had more than onecomorbid condition, with almost one in five having three or moreadditional conditions. Increasing levels of comorbidity wereassociated with more unscheduled health service utilisation forasthma, both in terms of hospital admissions (a greater thanthree-fold increase), and outpatient care (greater than two-foldincrease).

This study1 confirms and builds on the small number of previousstudies on asthma and comorbidity, and is generally in line withprevious findings. As the authors rightly state, the phenomenon ofcomorbidity in asthma warrants further study in terms of underlyingmechanisms, drug-drug interactions, effects on quality of life, andimplications for management – including self-management. Asthma isa common condition, and thus the implications of a heavy burden ofcomorbidity are important in terms of population health andhealthcare costs. Importantly, the study also demonstrated high levelsof comorbidity in young as well as older patients, suggesting thatwithout effective interventions such younger comorbid asthmaticsmay be on a trajectory towards high burden (and high cost)multimorbidity as they age. The fact that comorbidity was found to besocially patterned, being highest in those of lowest educational status,is also important with respect to health inequalities and the apparentlyever widening gap between rich and poor.2

It is also important to place these findings within the growingresearch and policy focus on multimorbidity. Comorbidity – as in thestudy by Stepphun et al.1 – is defined as an index condition plusadditional conditions, whereas multimorbidity – a term beingincreasingly used – is simply defined as the co-existence of two ormore conditions within an individual without any single disease beingthe focus.3 This may be a more useful term in primary care given thelongitudinal nature of the care provided and the fact that theimportance of any one condition may wax and wane over the life-course. In a recent nationally representative study of almost 1.8 millionpeople of all ages in Scotland (about one third of the population) wefound that multimorbidity affected one in four people.4 Out of the 40chronic conditions studied, including asthma, there was no conditionin which most people had that condition only.

Thus multimorbidity is the norm, not the exception, in chronicdisease. It is also the norm for most of the elderly population. Yet, asSteppuhn and colleagues also point out for asthma, a single-diseaseparadigm dominates healthcare policy, delivery and training.Guidelines are based on evidence from unusual people who only havea single condition; most randomised controlled trials (RCTs) excludepatients with other conditions. Therefore, the relevance of guidelinesto most people with most chronic conditions is questionable. Thegrowth of single-disease guidelines (which suggest when to start newmedications but seldom when to stop) together with the rise inmultimorbidity prevalence (in part due to the ageing population), isresponsible for the burgeoning rise in polypharmacy.5 Not allpolypharmacy is bad,6 but it does often result in poorer adherence tomedication, increases the risk of serious drug-drug and drug-diseaseinteractions, and adds to treatment burden.5,7,8

The increased risk of depression in asthma reported by Steppuhnand colleagues is well recognised in a wide-range of chronicconditions.9 The risk of depression rises as the level of multimorbidityincreases.4 Once again, this is heavily socially patterned, with thoseliving in more deprived areas having a higher risk of an associatedmental health problem as the number of physical conditionsincreases.4 Such clinical complexity calls for a generalist approach,compounded in deprived areas by the continuing existence of the‘inverse care law’.10

Interventions targeted specifically at patients with comorbidityand multimorbidity are desperately needed. A recent systematicreview found only a handful of intervention studies worldwide thatfocused on multimorbid patients, with disappointing outcomes.11

Complex clinical situations (involving comorbid or multimorbidpatients) almost certainly require complex interventions, and researchbodies must begin to fund such studies.

Conflicts of interest The author declares that he has no conflicts of interestin relation to this article.

Commissioned article; not externally peer reviewed; accepted 10th February 2014;online 19th February 2014

Comorbidity in asthma is important and requires a generalistapproach

*Stewart W Mercer1

1 Professor of Primary Care Research, Department of General Practice and Primary Care, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK

*Correspondence: Professor Stewart W Mercer, Department ofGeneral Practice and Primary Care, Institute of Health andWellbeing, University of Glasgow, 1 Horseletthill Road, GlasgowG12 9LX, UKTel: +44 0141 330 8330 Fax: +44 0141 330 8331 E-mail: stewart.mercer@glasgow.ac.uk

See linked article by Stepphun et al. on pg 22

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© 2014 Primary Care Respiratory Society UK. All rights reservedhttp://dx.doi.org/10.4104/pcrj.2014.00012Prim Care Respir J 2014; 23(1): 4-5

References 1. Steppuhn H, Langen U, Keil T, Scheidt-Nave C. Chronic disease co-morbidity of

asthma and unscheduled asthma care among adults: results of the national

telephone health interview survey German Health Update (GEDA) 2009 and 2010.

Prim Care Respir J 2014;23(1):22-29. http://dx.doi.org/10.4104/pcrj.2013.00107

2. Commission on Social Determinants of Health, Closing the gap in a generation.

Health equity through action on the social determinants of health. 2008, World

Health Organisation: Geneva.

3. van den Akker M, Buntinx F, Knottnerus JA. Comorbidity or multimorbidity: what's

in a name? A review of literature. Eur J Gen Pract 1996;2:65-70.

http://dx.doi.org/10.3109/13814789609162146

4. Barnett, K., S. Mercer, et al. Epidemiology of multimorbidity and implications for

health care, research, and medical edication: a cross-sectional study. Lancet

2012;380(9836):37-43. http://dx.doi.org/10.1016/S0140-6736(12)60240-2

5. Guthrie B, Payne K, Alderson P, McMurdo MET, Mercer SW. Adapting clinical

guidelines to take account of multimorbidity. BMJ 2012;345:e6341.

http://dx.doi.org/10.1136/bmj.e6341

6. Payne RA, Abel GA, Avery AJ, Mercer SW, Roland MO. Is polypharmacy always

hazardous? A retrospective cohort analysis using linked electronic health records

from primary and secondary care. Br J Clin Pharmacol 2014, Jan 15 [Epub ahead of

print] http://dx.doi.org/10.1111/bcp.12292

7. Vik SA, Maxwell CJ, Hogan DB. Measurement, correlates, and health outcomes of

medication adherence among seniors. Ann Pharmacother 2004;38:303-12.

http://dx.doi.org/10.1345/aph.1D252

8. May C, Montori VM, Mair FS. We need minimally disruptive medicine. BMJ 2009;

339:b2803. http://dx.doi.org/10.1136/bmj.b2803

9. National Institute for Health and Clinical Excellence. Depression in adults with a

chronic physical health problem: treatment and management (National Clinical

Practice Guideline Number 91 ).

10. Mercer SW, Guthrie B, Furler J, Watt GCM, Hart JT. Multimorbidity and the inverse

care law in primary care. BMJ 2012;344:e4152.

http://dx.doi.org/10.1136/bmj.e4152

11. Smith SM, Soubhi H, Fortin M, Hudon C, O’Dowd T. Interventions for improving

outcomes in patients with multimorbidity in primary care and community settings:

systematic review. BMJ 2012;345:e5205. http://dx.doi.org/10.1136/bmj.e5205

In this issue of the PCRJ, Boland et al. report an assessment of theold and new GOLD COPD classifications using a large cohortobtained from 28 Dutch primary care centres.1 In a way, weSpaniards could compare this Dutch GOLD assessment with thegoal from Andrés Iniesta who scored deep into extra-time to giveSpain victory over the Netherlands in the World Cup final atSoccer City in Johannesburg in 20102 after an exciting butgoalless first 114 minutes… (see Figure 1, available online atwww.thepcrj.org).

On November 16th 2011, the current revision of the GOLDExecutive Summary was released in Shanghai, China,3 and laterpublished elsewhere.4 It presented a new classification of COPD whichwas intended to provide a better understanding of the impact of thedisease on an individual patient than the previous spirometry-onlyCOPD staging. The four previous spirometry categories were reduced

to two, and information on exacerbations and symptoms was addedto form a three-dimensional patient evaluation.

This new Dutch research1 should be commended, as it showcasesa true real-life COPD management assessment. The GOLD Committeeshould be happy to see that more investigators are independentlyvalidating their new recommendations, with this study being added tothe growing list of replications, most of which show consistentfindings.5 In a population with generally mild COPD – as it is often thecase (but not always) in primary care – Boland et al. conclude that “…the GOLD ABCD groups classification is more closely associated withcosts and HRQoL [health-related quality of life] than the GOLD 1234grades classification. Furthermore, patients with GOLD-C had a betterHRQoL than those with GOLD-B but the costs of the two groups didnot differ.” This is good news indeed for GOLD; the new GOLD ABCDstaging relates very well with increasing costs, and also with bothdisease- and generic-HRQoL. However, even in this primary carepopulation, patient symptoms in groups B and D produceinconsistencies in staging. There are also novel and very importantfindings here on comorbidities.1 GOLD clearly indicates the relevanceof COPD comorbidities in their latest updates, and these primary careCOPD patients in stages GOLD B and D have more comorbidities, lessphysical activity and self-efficacy, and more unemployment.

The strengths of this research from Boland et al.1 include novelty;there are only a handful of assessments available in primary care,6-9

mostly with consistent findings that neither age nor gender should beassociated with the GOLD severity distribution. The study also includesa comprehensive cost-associated analysis (which includes travel costs)from a prestigious, experienced group of researchers, as well as verysophisticated statistics (which are not for the mere mortal clinicalreader…). There is also a comprehensive online appendix withextensive sub-analyses. All in all, this study1 should indeed stimulate

A golden goal in 2010, and another GOLD in 2014 in primary care, or vice versa

*Joan B Soriano1, Miguel Román-Rodríguez2

1 Medical Epidemiologist, FISIB-IdISPA Hospital Universitari Son Espases, Palma de Mallorca, Spain

2 General practitioner, Centre de Salut de Son Pizà, Palma de Mallorca, Spain

*Correspondence: Dr Joan B Soriano, FISIB-IdISPA HospitalUniversitari Son Espases, Unitat Assaigs Clínics Mòdul I, Nivel -1,Despatx 2, Carretera de Valldemossa, 79; 07010 Palma deMallorca, EspañaTel: +34 871 205000 Ext 65720 Fax: +34 871 206868E-mail: jbsoriano2@gmail.com

See linked article by Boland et al. on pg 30

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thinking on patient-centred outcomes, and is a significant steptowards personalised medicine.

However, some limitations should also be noted – i.e.representativeness and misdiagnosis. As a true real-world assessment,Boland et al.’s Figure 11 indicates that less than half of thoseapproached finally participated, so a non-response study might bewelcome. Also it is stated that 29.6% (575/2006) were found to bemisdiagnosed with COPD. It is likely therefore that both issues makean impact on the severity distribution (over 50% are GOLD A and only14 COPD participants are GOLD D3). Heterogeneity among the 28practices must be expected. In terms of quality of life assessment,there was no CAT score used in this research and the SGRQ has beenused as an outcome measure. Such re-categorisation when producedby different methods (e.g. using CAT, or mMRC dyspnoea scale, CCQ,or other), might produce very different groupings, and thereforecategories might not be internally consistent. Finally, the workingdefinition of acute exacerbation of COPD is sui generis (i.e. unique).

Meanwhile, some practical questions remain for GPs to answer. Isthe new GOLD staging being implemented in primary care? What arethe hurdles? Regrettably, after so many years and different versions,there is still no primary care representation included in the GOLDguideline. It has recently been argued that any new treatmentalgorithm aimed at primary care clinicians should fully involvemembers of this community in its production, and should be pilotedand evaluated rigorously in primary care settings beforedissemination.10 As per the new Spanish GESEPOC COPDguidelines,11,12 a multicomponent assessment of COPD severity (withinprimary care or elsewhere) should take into account a range of itemsincluding spirometry, smoking, exacerbations, health status, andcomorbidities. This could be done using multi-component indices suchas BMI, airflow Obstruction, Dyspnoea, and Exercise capacity (BODE),or its modifications, or other.

Pooling together Boland et al.’s primary care data1 with otherCOPD GOLD replications obtained in specialised settings will likely beextremely useful,5,13 allowing clinically- and very practically-orientedsub-analyses, thus encompassing all respiratory effectivenessassessments.14 Already, the current COPD Cohorts CollaborativeInternational Asssessment (3CIA) initiative, aimed at pooling Europeanand other COPD cohorts, might explore further new, objectively-obtained respiratory endpoints and thresholds.15

Back to the beautiful game; things would be very different ifGOLD included primary care players in its team, or if Arjen Robben’sclear chance had not been lost in the 68th minute as he left Puyol andPiqué in his wake before “Saint” Casillas smothered the ball with theedge of his right foot. From now onwards, the rest is history to bewritten…

Conflicts of interest The authors declare that they have no conflicts ofinterest in relation to this article.

Commissioned article; not externally peer reviewed; accepted 13th February 2014;online 28th February 2014© 2014 Primary Care Respiratory Society UK. All rights reservedhttp://dx.doi.org/10.4104/pcrj.2014.00018Prim Care Respir J 2014; 23(1): 5-6

References 1. Boland MRS, Tsiachristas A, Kruis AL, Chavannes NL, Rutten-van Mölken MPMH.

Are GOLD ABCD groups better associated with health status and costs than GOLD

1234 grades? A cross-sectional study. Prim Care Respir J 2014;23(1):30-37.

http://dx.doi.org/ 10.4104/pcrj.2014.00002

2. World Cup Final 2010 Highlights Spain vs Netherlands (Espana vs Netherlands)

http://www.youtube.com/watch?v=NTIlZoGp68I

3. GOLD press release. Summary handout of a GOLD conference sponsored by the

Asian Pacific Society of Respirology in Shanghai, China, November 6, 2011.

[Accessed on April 10th, 2013 at http://www.goldcopd.org/uploads/users/files/

GOLD2011_Summary.pdf ]

4. Vestbo J, Hurd SS, Agustí AG, et al. Global Strategy for the Diagnosis,

Management, and Prevention of Chronic Obstructive Pulmonary Disease: GOLD

Executive Summary. Am J Respir Crit Care Med 2013;187:347-65.

http://dx.doi.org/10.1164/rccm.201204-0596PP

5. Soriano JB. The GOLD Rush. Thorax 2013;68(10):902-03.

http://dx.doi.org/10.1136/thoraxjnl-2013-203595

6. Haughney J, Gruffydd-Jones K, Roberts J, Lee AJ, Hardwell A, McGarvey L. The

distribution of COPD in UK general practice using the new GOLD classification. Eur

Respir J 2013 Epub Oct 31, erj 00650-2013.

http://dx.doi.org/10.1183/09031936.00065013

7. Jones PW, Nadeau G, Small M, Adamek L. Characteristics of a COPD population

categorised using the GOLD framework by health status and exacerbations. Respir

Med 2014;108(1):129-35. http://dx.doi.org/10.1016/j.rmed.2013.08.015

8. Punekar YS, Shukla A, Müllerova H. COPD management costs according to the

frequency of COPD exacerbations in UK primary care. Int J Chron Obstruct Pulmon

Dis 2014;9:65-73. http://dx.doi.org/10.2147/COPD.S54417

9. Maio S, Baldacci S, Martini F, et al. on behalf of the COMODHES study group.

COPD management according to old and new GOLD guidelines: an observational

study with Italian general practitioners. Curr Med Res Opin 2014. Epub Feb 3.

http://dx.doi.org/10.1185/03007995.2014.884492

10. Jones R, Price D, Chavannes N, et al. GOLD COPD categories are not fit for purpose

in primary care. Lancet Respir Med 2013;1(1):e17.

http://dx.doi.org/10.1016/S2213-2600(13)70015-8 Epub 2013 Mar 4. No abstract

available.

11. Grupo de Trabajo de GesEPOC . Guía de Práctica Clínica para el Diagnóstico y

Tratamiento de Pacientes con Enfermedad Pulmonar Obstructiva Crónica (EPOC) -

Guía Española de la EPOC (GesEPOC). Arch Bronconeumol 2012;48( suppl 1):1- 83.

12. Miravitlles M, Soler-Cataluña JJ, Calle M, et al. A new approach to grading and

treating COPD based on clinical phenotypes: summary of the Spanish COPD

guidelines (GesEPOC). Prim Care Respir J 2013;22(1):117-21.

http://dx.doi.org/10.4104/pcrj.2013.00016

13. Riley RD, Lambert PC, Abo-Zaid G. Meta-analysis of individual participant data:

rationale, conduct, and reporting. BMJ 2010;340:c221.

http://dx.doi.org/10.1136/bmj.c221.

14. Roche N, Reddel HK, Agusti A, et al. Respiratory Effectiveness Group. Integrating

real-life studies in the global therapeutic research framework. Lancet Respir Med

2013;1(10):e29-30. http://dx.doi.org/10.1016/S2213-2600(13)70199-1

15. Almagro P, Martinez-Camblor P, Soriano B et al. Finding the best thresholds of FEV1

and dyspnea to predict 5-year survival in COPD patients: the COCOMICS study.

PLOS ONE 2014 (in press; reference PONE-D-13-39114).

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The computerisation of clinical patient records in primary careprovides an opportunity to collect health care data at nationaland international level. There is a dawning awareness of theenormous potential of such data, both as a research tool and asa means to improve the quality of health care provision. Forcommissioners and service planners there is a golden opportunityto lead the way in the constructive use of data to the benefit ofboth clinicians and patients.

Such an example is the exploitation of routinely collected datafrom primary care for research. From the august origins of the GeneralPractice Research Database, a plethora of datasets are now availablewith data on demographics, diagnoses, tests, treatments andoutcomes. Researchers can now link general practice data with datafrom other sources such as hospital statistics and national registers ofcancer and death, thus providing huge potential for the study ofdisease prevalence, interaction of co-morbidities, and impacts onoutcomes.

Gathering data from multiple primary care sources remains achallenge, however, and this is being addressed in various ways. TheScandinavian countries have developed large datasets using diseaseregistries, notably for COPD, which provide access to massivelongitudinal data. International researchers such as those involved inthe UNLOCK1 study and the Respiratory Effectiveness Group, arecombining large datasets to answer specific questions. Ground ruleson methodology and use in guidelines are being set.2 From this therehas emerged a series of projects – e.g. the evaluation of the propertiesof prognostic indices.3

A second use of large datasets is for clinical audit, which involveseither collection of data and/or analysis of existing data sources tobring about quality improvements in health care. In this way, variationin health care between areas4 and individual providers can beidentified, and by benchmarking against standards remedial actioncan be targeted at poor performers.

Finland has been an exemplar of true audit, with a coordinatednational COPD multidisciplinary education and health improvementintervention informed by clinical data.5 A series of national datacollections carried out over a 10-year period demonstrated sustainedquality improvement and a reduction in hospital admissions.

In this issue of the PCRJ, Ställberg et al. report the findings from aSwedish national register study with a representative sample of datacollected prospectively for 11 years on 21,000 patients with COPDfrom 76 primary care centres.6 Primary care data was linked to deathregisters yielding influential studies on disease management andprognosis.7,8 Over time this audit has demonstrated clearimprovements in the quality of care received by these COPD patientsin Sweden.

A strength of the Ställberg study was the use of well recordedclinical computerised notes with searchable codes. However, not allitems were routinely recorded – for example, only one-third hadsmoking data and only 29% had data on spirometry. Recordedsmoking data was likely to be of high quality, but the data may be oflesser quality for items such as spirometry, which is affected by theexpertise of the operator. Exacerbation recording is crucial, but oftenpoorly documented; in this study the authors used a sensibleapproach, using a composite method to estimate exacerbationfrequency – admissions or oral steroid or oral antibiotics prescribed“because of respiratory symptoms”.

Improving data recording and data quality are vital audit aims. TheFinnish experience is that data collection used to define educationinterventions coupled with feedback and support when delivered as aholistic programme does make a difference to the quality of carereceived by COPD patients.

Within the UK, audit has been central to the use of datasets andquality improvement, but there have been disappointing results forCOPD secondary care.9 A new national audit of England and Wales isbeing launched this year, which will collect data from across primaryand secondary care. What learning from the Swedish6 and Finnish5

experience can be used to improve the impact of this initiative? The England and Wales COPD audit is an ambitious 5-year

programme led by a consortium of professional, patient and carerorganisations. There are three main work streams – Primary Care,Hospital Care, and Pulmonary Rehabilitation – together with a 12-month feasibility study of the collection of Patient ReportedExperience Measures across all three work streams. It is hoped thatdata from around 750,000 people with COPD will be collected in2014. The primary care audit measures include key processes of careand patient outcomes. Data will be blueprinted against nationalguidance.10,11 Electronic codes will be used to identify relevant datawithin General Practice clinical systems from which process items andoutcomes will be extracted by the Health and Social Care InformationCentre. These data will in turn be linked to other national data sourcesusing UK National Health Service (NHS) patient numbers as a uniqueidentifier, then pseudo-anonymised for analytical purposes. Patient

National cohort data from Sweden to the National COPD auditin England and Wales: grand designs for quality improvement

*Rupert Jones1, Michael Roberts2

1 Clinical Research Fellow, Plymouth University Peninsula Schools of Medicine and Dentistry, Plymouth, UK; General Practitioner, Armada Surgery, Plymouth, UK

2 Dean, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK; Head, UK National COPD Audit Programme

*Correspondence: Dr Rupert Jones, Clinical Research Fellow,Plymouth University Peninsula Schools of Medicine andDentistry, 1 Davy Road (N21), Plymouth, PL6 8BX, UKTel & Fax: +44 01752 764259E-mail: rupert.jones@plymouth.ac.uk

See linked article by Stallberg et al. on pg 38

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data will be linked across the three audit work streams and will beanalysed centrally. Reports with benchmarking against the nationalaverage will be provided for all participating practices, with higherlevel reports for commissioners and other organisations at a regionaland national level. The practice reports will offer support forstandardised coding of records and service improvement. Changes willbe measured in repeat audit cycles.

Whilst the collection of this database in England and Wales is itselfa massive undertaking, the learning from Finland5 is that this is merelythe beginning of a 5-year quality improvement programme. Withinsecondary care a peer review initiative is one option to driveimprovements in care. For pulmonary rehabilitation programmes, anaccreditation process is proposed which could drive up standards andassist commissioning of rehabilitation. One of the underlyingprinciples of all such national audits is the open publication of data.This may be used to help patients and commissioners to understandthe quality of services available.

The Swedish6 and Finnish5 National studies have shown what canbe accomplished if a national effort is made to collect good qualitydata and to use those data to support clinicians in improving thequality of care delivered to COPD patients. We now plan to collect amuch bigger dataset in England and Wales and use this to drive amulti-faceted quality improvement programme on the care of ourCOPD patients. This is an opportunity for clinicians to deliver a longoverdue UK national health improvement programme on a grandscale for a previously neglected group of people.

Conflicts of interest The authors declare that they have no conflicts ofinterest in relation to this article.

Commissioned article; not externally peer reviewed; accepted 4th February 2014;online 19th February 2014© 2014 Primary Care Respiratory Society UK. All rights reservedhttp://dx.doi.org/10.4104/pcrj.2014.00013Prim Care Respir J 2014; 23(1): 7-8

References 1. Chavannes N, Stallberg B, Lisspers K, et al. UNLOCK: Uncovering and noting long-

term outcomes in COPD to enhance knowledge. Prim Care Respir J 2010;19(4):

408. http://dx.doi.org/10.4104/pcrj.2010.00084

2. Price D, Hillyer EV, van der Molen T. Efficacy versus effectiveness trials: informing

guidelines for asthma management. Current Opinion in Allergy and Clinical

Immunology 2013;13(1):50-7. http://dx.doi.org/10.1097/ACI.0b013e32835ad059

3. Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk

of serious pneumonia. Thorax 2013;68(11):1029-36.

http://dx.doi.org/10.1136/thoraxjnl-2012-202872

4. Observatory ERPH. NHS Atlas of Variation in Healthcare for People with Respiratory

Disease 2012.

5. Kinnula VL, Vasankari T, Kontula E, Sovijarvi A, Saynajakangas O, Pietinalho A. The

10-year COPD Programme in Finland: effects on quality of diagnosis, smoking,

prevalence, hospital admissions and mortality. Prim Care Respir J 2011;20(2):178-

83. http://dx.doi.org/10.4104/pcrj.2011.00024

6. Ställberg B, Janson C, Johansson G, Larsson K, Stratelis G, Telg G, Lisspers KH.

Management, morbidity and mortality of COPD during an 11-year period: an

observational retrospective epidemiological register study in Sweden (PATHOS).

Prim Care Respir J 2014;23(1):38-45. http://dx.doi.org/10.4104/pcrj.2013.00106

7. Janson C, Larsson K, Lisspers KH, et al. Pneumonia and pneumonia related

mortality in patients with COPD treated with fixed combinations of inhaled

corticosteroid and long acting β2 agonist: observational matched cohort study

(PATHOS). BMJ 2013;346:f3306. http://dx.doi.org/10.1136/bmj.f3306.

8. Sundh J, Janson C, Lisspers K, Stallberg B, Montgomery S. The Dyspnoea,

Obstruction, Smoking, Exacerbation (DOSE) index is predictive of mortality in

COPD. Prim Care Respir J 2012;21(3):295-301.

http://dx.doi.org/10.4104/pcrj.2012.00054

9. George PM, Stone RA, Buckingham RJ, Pursey NA, Lowe D, Roberts CM. Changes

in NHS organization of care and management of hospital admissions with COPD

exacerbations between the national COPD audits of 2003 and 2008. QJM

2011;104(10):859-66. http://dx.doi.org/10.1093/qjmed/hcr083

10. Department of Health. An outcomes strategy for people with chronic obstructive

pulmonary disease (COPD) and asthma in England. London, 2011.

11. The National Institute for Health and Clinical Excellence. Chronic Obstructive

Pulmonary Disease Quality standard advice to the Secretary of State for Health.

London, 2011.

Hospice/palliative care is not just end-of-life care, it is specialisedmedical care for patients with serious illness.1 Althoughdefinitions of “serious illness” may vary, it is clear that far morepatients could benefit from hospice/palliative care than we canactually serve, given the existing workforce challenges and thelack of clarity in how to pay for specialist palliative carethroughout the world. The needs of patients and caregivers aresimilar regardless of the underlying life limiting illness.2-4

On Goldilocks, care coordination, and palliative care: making it‘just right’

Thomas W LeBlanc1,2, David C Currow3, *Amy P Abernethy2,4

1 Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke University School of Medicine, Durham, NC USA

2 Center for Learning Health Care, Duke Clinical Research Institute,Durham, NC USA

3 Discipline, Palliative and Supportive Services, Flinders University, Adelaide, Australia

4 Division of Medical Oncology, Department of Medicine, Duke University School of Medicine, Durham, NC USA

See linked article by Epiphaniou et al. on pg 46 *Correspondence: Dr Amy Abernethy, Box 3436, DukeUniversity Medical Center, Durham, NC 27710Tel: 919 668 0647 Fax: 919-681-7985E-mail: amy.abernethy@duke.edu

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Appropriate timing of referrals is key, but this timing must beclearly defined for each disease group, with differences to be expectedbetween cancer and COPD.5 Not every patient needs to see apalliative care specialist, and the timing matters greatly whenresources are limited.6 Thus, as palliative care continues to movefurther upstream in a patient’s journey, these limitations necessitatethat we be better able to match the right type of care with the rightpatient at the right time. Models of “care coordination” offer onepotentially promising strategy for addressing this problem.

In this issue of the PCRJ, Epiphaniou and colleagues7 report theresults of a longitudinal qualitative study of patients’ experiences withend-of-life care coordination in the UK. These results highlight severalimportant truths about the current state of care coordination. First,patients with COPD had little access to care coordinators (or“keyworkers” as they are called here). These patients are at risk forincreasingly frequent re-hospitalisations as the disease progresses, andavoiding hospital is a crucial way of improving care and decreasinghealthcare costs. Given the very long illness trajectory for people withCOPD,8 they may seem less in need of care coordination, and areoften left without easy access to close follow-up care after hospitaldischarge. Patients with COPD in this study expressed a sense offeeling left out on their own without much support.

Patients with lung cancer, on the other hand, routinely had accessto a care coordinator.7 Among those who did, nearly all felt it wasvaluable. These findings highlight the remarkably positive role carecoordinators can play in the life of a patient with serious illness.Patients frequently described how useful the coordinator was inresponding to their needs by matching them with various services,and helping them contact their physicians. The complex care neededfor those with advanced illness can be very overwhelming andpatients may need a “disease shepherd” to help show them the way.

These key concepts of care coordination are central to the carethat is provided by hospice/palliative care services around the world.Such care might be expected to result in fewer emergencydepartment visits or hospital stays for patients with serious,progressive illnesses. Interestingly, despite its intuitive appeal, carecoordination actually does not always result in improved outcomes. Infact, published studies have been somewhat mixed. For example, asimilar concept was tested in the US cancer setting, using “nursenavigators.”9 In a randomised controlled trial, this intervention yieldedimprovements in psychosocial care, care coordination, and patientinformation, but actually did not improve quality of life. It also did notreduce costs, except in a subset with lung cancer. Similarly, in a largerandomised trial of a tele-health intervention for patients with COPD,10

a daily symptom and medication monitoring approach was noteffective in reducing re-hospitalisations or improving quality of life.Though slightly different from care coordinators, this finding putsforward the challenge of how best to apply findings from the study byEpiphaniou et al.7 to populations of people with COPD.

Another noteworthy study of care coordination is the “PalliativeCare Trial.”11,12 Here, the implementation of a single patient-focusedcase conference, coordinated by a palliative care nurse in concert withthe general practitioner (GP), was shown to reduce hospitalisations by26% and to provide better maintenance of performance status. The

nurse and GP assessed the patient’s needs and translated these to themultidisciplinary case conference, bringing the patient’s voice to theplan of care. This approach embodies the “disease shepherd” modelby helping match the right support services to the right patient in atimely way. Referrals and use of scarce resources are thus based onneed, rather than diagnosis or prognosis. As so conceived, a carecoordinator may be the very steward that we need to judiciouslyexpand palliative care services to those patients who are particularlylikely to need and/or benefit from accessing them.

In heart failure, a nurse-led intervention comprisingcomprehensive education, social-service consultation, and intensivefollow-up reduced 90-day heart failure readmission by 56.2%,improved quality of life, and reduced the cost of care.13 A meta-analysis of published trials of post-discharge support strategies furthersupports these findings.14 In contrast, enhanced access to primary carefor heart failure patients did not improve their self-reported healthstatus and was actually associated with more frequenthospitalisation.15 Reconciling these findings will be important inmoving science forward in this area.

In the end, what do these somewhat contradictory results meanfor hospice/palliative care, and for clinicians who face the difficultdecision about timing a referral or who are trying to adopt a model ofcare coordination? Wherein lies the “transition point” – the“Goldilocks point” – where it is exactly the right time to mobilisespecialist hospice/palliative care services for the patient sub-group whowill derive the most benefit? Whilst we do not pretend to have all theanswers, we do propose a path forward in terms of further research.More work is needed to explore the role of functional limitations, theonset of troublesome symptoms, or both, as a potentially usefulthreshold to trigger further care coordination. The onset of functionaldecline often portends a poor prognosis, especially in cancer settings,16

and symptoms often signal an impending need for emergency orinpatient services. Symptoms can now be monitored in the homeusing emerging technological applications,17 and once decline isnoted, care coordination could be mobilised to assess the potentialneed for additional services. More active use of mobile healthtechnology solutions is likely to play an important role in solving thispuzzle, helping us match the right care to the right patient at the righttime. Care coordinators will not fix all of palliative care’s serviceplanning problems, but are a key part of the solution if appropriatelyapplied. Regardless, further study is needed not only on their impacton patients, but also on patients’ caregivers.

Acknowledgement The authors acknowledge Donald T. Kirkendall, ELS, aDuke-employed medical editor, for his assistance in the preparation of this editorial.Conflicts of interest Dr. Abernethy, the current President of the AmericanAcademy of Hospice and Palliative Medicine, reports board memberships (Advoset,Orange Leaf Associates, Athena Health); consultancies (Pfizer, Novartis, Helsinn,Bristol Myers Squibb); and grant support (Pfizer, Helsinn, Kanglaite, DARA, MiCo,NINR, NIA, NCI, AHRQ, Medical College of Wisconsin, Memorial Sloan KetteringCancer Center, Sanofi, Bristol Myers Squibb, Denderon, Alliance for Clinical Trials inOncology). Funding Dr. LeBlanc is a recipient of a Junior Career Development Award Grantfrom the National Palliative Care Research Center (NPCRC). Dr. Currow receivesgrant support from the National Health and Medical Research Council and from theFlinders Medical Center Foundation of Bedford Park S. Australia.

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Commissioned article; not externally peer reviewed; accepted 11th February 2014;online 19th February 2014© 2014 Primary Care Respiratory Society UK. All rights reservedhttp://dx.doi.org/10.4104/pcrj.2014.00017Prim Care Respir J 2014; 23(1): 8-10

References 1. Quill TE, Abernethy AP. Generalist plus specialist palliative care--creating a more

sustainable model. N Engl J Med 2013;368(13):1173-5.

http://dx.doi.org/10.1056/NEJMp1215620

2. Luddington L, Cox S, Higginson I, Livesley B. The need for palliative care for

patients with non-cancer diseases: a review of the evidence. Int J Palliat Nurs

2001;7(5):221-6.

3. Currow DC, Ward A, Clark K, Burns CM, Abernethy AP. Caregivers for people with

end-stage lung disease: characteristics and unmet needs in the whole population.

Int J Chron Obstruct Pulmon Dis 2008;3(4):753-62.

4. Girgis A, Abernethy AP, Currow DC. Caring at the end of life: do cancer caregivers

differ from other caregivers? BMJ Support Palliat Care 2014;Published Online First

22 January 2014. http://dx.doi.org/10.1136/bmjspcare-2013-000495

5. Curtis JR. Palliative and end-of-life care for patients with severe COPD. Eur Respir J

2008;32(3):796-803. http://dx.doi.org/10.1183/09031936.00126107

6. Currow DC, Abernethy AP, Fazekas BS. Specialist palliative care needs of whole

populations: a feasibility study using a novel approach. Palliat Med 2004;18(3):239-

47. http://dx.doi.org/10.1191/0269216304pm873oa

7. Epiphaniou C, Shipman C, Harding R, Mason B, Murray SAA, Higginson IJ, Daveson

BA. Coordination of end-of-life care for patients with lung cancer and those with

advanced COPD: are there transferable lessons? A longitudinal qualitative study.

Prim Care Respir J 2014;23(1):46-51. http://dx.doi.org/10.4104/pcrj.2014.00004

8. Currow DC, Plummer JL, Crockett A, Abernethy AP. A community population

survey of prevalence and severity of dyspnea in adults. J Pain Symptom Manage

2009;38(4):533-45. http://dx.doi.org/10.1016/j.jpainsymman.2009.01.006

9. Wagner EH, Ludman EJ, Aiello Bowles EJ, et al. Nurse navigators in early cancer

care: a randomized, controlled trial. J Clin Oncol 2014;32(1):12-18.

http://dx.doi.org/10.1200/JCO.2013.51.7359

10. Pinnock H, Hanley J, McCloughan L, et al. Effectiveness of telemonitoring

integrated into existing clinical services on hospital admission for exacerbation of

chronic obstructive pulmonary disease: researcher blind, multicentre, randomised

controlled trial. BMJ 2013;347:f6070. http://dx.doi.org/10.1136/bmj.f6070

11. Abernethy AP, Currow DC, Hunt R, et al. A pragmatic 2 x 2 x 2 factorial cluster

randomized controlled trial of educational outreach visiting and case conferencing

in palliative care-methodology of the Palliative Care Trial [ISRCTN 81117481].

Contemp Clin Trials 2006;27(1):83-100.

http://dx.doi.org/10.1016/j.cct.2005.09.006

12. Abernethy AP, Currow DC, Shelby-James T, et al. Delivery strategies to optimize

resource utilization and performance status for patients with advanced life-limiting

illness: results from the "palliative care trial" [ISRCTN 81117481]. J Pain Symptom

Manage 2013;45(3):488-505.

http://dx.doi.org/10.1016/j.jpainsymman.2012.02.024

13. Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM. A

multidisciplinary intervention to prevent the readmission of elderly patients with

congestive heart failure. N Engl J Med 1995;333(18):1190-5.

http://dx.doi.org/10.1056/NEJM199511023331806

14. Phillips CO, Wright SM, Kern DE, Singa RM, Shepperd S, Rubin HR. Comprehensive

discharge planning with postdischarge support for older patients with congestive

heart failure: a meta-analysis. JAMA 2004;291(11):1358-67.

http://dx.doi.org/10.1001/jama.291.11.1358

15. Oddone EZ, Weinberger M, Giobbie-Hurder A, Landsman P, Henderson W.

Enhanced access to primary care for patients with congestive heart failure. Veterans

Affairs Cooperative Study Group on Primary Care and Hospital Readmission. Eff

Clin Pract 1999;2(5):201-09.

16. Suh SY, Leblanc TW, Shelby RA, Samsa GP, Abernethy AP. Longitudinal patient-

reported performance status assessment in the cancer clinic is feasible and

prognostic. J Oncol Pract 2011;7(6):374-81.

http://dx.doi.org/10.1200/JOP.2011.000434

17. Kumar S, Nilsen WJ, Abernethy A, et al. Mobile health technology evaluation: the

mHealth evidence workshop. Am J Prev Med 2013;45(2):228-36.

http://dx.doi.org/10.1016/j.amepre.2013.03.017

Every general practitioner (GP) knows that many young childrenwheeze during upper respiratory tract infections, and that mostof these children do not become asthmatic later duringchildhood. Data from population-based studies show that one inthree children will have at least one episode of wheezing during

the first three years of life.1 Two-thirds of these preschoolwheezers outgrow their symptoms by the age of six, and theremaining third develop asthma.1,2 Wouldn’t it be great if wecould predict which preschool wheezer will become asthmaticand which will not? Such knowledge would not only be useful forcounselling parents, but could also be used to target therapy.Given our ongoing concerns over the safety of inhaledcorticosteroids, particularly in young children,3 we prefer to avoidtreating transient preschool wheezers unnecessarily with dailycontroller treatment for asthma.

Until recently, the knowledge about which factors were associatedwith the persistence or remittance of preschool wheeze came fromgeneral population birth cohort studies.1 The asthma predictive scoresbased on these studies show a statistically significant association withasthma and wheeze at age six years, but their value for predicting theoutcome of preschool wheeze in individual cases is poor.4 Since not allyoung children with wheeze are brought to their GP, the applicabilityof these asthma predictive scores in primary care is unclear. Inaddition, because parents use the word “wheeze” to describe a range

Predicting the outcome of early childhood wheeze: missionimpossible

*Paul LP Brand1

1 Amalia Children’s Centre, Isala Hospital, Zwolle, The Netherlands;UMCG Postgraduate School of Medicine, University Medical Centre and University of Groningen, The Netherlands

*Correspondence: Professor Paul LP Brand, Princess AmaliaChildren’s Centre, Isala Hospital, PO Box 10400, 8000 GKZwolle, the Netherlands.Tel: +31 38 4245050 Fax + 31 38 4247660E-mail: p.l.p.brand@isala.nl

See linked article by Cano-Garcinuño et al. on pg 60

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of respiratory sounds and phenomena in their children,5 and onlydoctor-confirmed wheeze is associated with airway obstruction inpreschool children,6 asthma prediction scores from population studiesshould be validated against doctor-confirmed wheeze in primary care.

In this issue of the PCRJ, Cano-Garcinuño and colleagues presentresults from a review of medical records of preschool children from 29primary care health centres in northern Spain.7 If the primary carephysician recorded wheeze on auscultation in the chart of a childpresenting with respiratory symptoms, this was defined as a wheezingepisode. Children were followed up to the age of six years. Data wereanalysed with innovative statistical techniques, comprising both latentclass analysis and linear joinpoint regression, allowing, in the words ofthe authors, “a high-resolution analysis of incidence”. The authorsconclude that such incidence analysis helps to clarify the naturalhistory of early childhood wheezing.

Let us examine their results in a little more detail. Almost half ofthe children (45.6%) had at least one episode of wheeze during thefirst three years of life, and 25% of these were diagnosed with activeasthma (a doctor’s diagnosis plus prescription of at least one anti-asthma drug) by the age of six years. Interestingly, the prevalence ofwheeze was considerably higher in this Spanish primary care studythan in two earlier population-based birth cohort studies from the UKand the Netherlands.8 This is unlikely to be caused by a smallerdenominator (i.e., not all children visiting their primary carepractitioner), since the primary care physician for children in Spain isthe community paediatrician who sees all children both for preventionpurposes (well baby visits and immunisations) and for symptoms orillness. It is also unlikely that the true population prevalence of wheezein young children is higher in Spain than in other western Europeancountries; previous work using parent-reported prevalence of wheezein young children showed slightly lower wheeze prevalence in Spainthan in the Netherlands.9 Spanish primary care paediatricians may thusbe more likely to record chest auscultation findings in young childrenas “wheeze” than their English and Dutch colleagues. These resultscall for further studies examining the differences between physiciansfrom different countries in their interpretation of chest auscultationfindings in young children.

Did the primary care setting of the study7 – with doctor-confirmedinstead of parent-reported wheeze – improve the value of clinical signsand symptoms in predicting asthma at age six? No. Almost half of thechildren with active asthma at age six (46.6%) belonged to thenever/infrequent wheeze group in the first three years of life (childrenwho had never (74%) or very infrequently wheezed (never more thanthree wheezing episodes, 26%). The sensitivity of wheeze pattern inearly life for predicting asthma was therefore poor. Likelihood ratioswere also too small to be clinically useful. The incidence patterns ofwheeze identified in this Spanish study are insufficiently distinctive toallow reliable prediction of the outcome of early childhood wheeze.Very recently, data from the Leicester birth cohort study have shownsimilar results.10 Simple clinical characteristics – such as wheeze not

associated with a cold, wheeze frequency, disturbance of activities,personal history of eczema, and family history of atopy – helped a littlebit, but not much, in predicting the outcome of early childhoodwheeze presenting to a GP.10

Experienced GPs know this already. They also know that you cannever tell in an individual case. This is likely due to the multifactorialnature of both early childhood wheeze and childhood asthma, whichare both only partly understood. I think it extremely unlikely that anyother prospective cohort study using only clinical characteristics andperhaps some lung function and allergic sensitisation data is going tochange this. Unless we find a better way to understand the genetic,immunologic, functional and pathological mechanisms of preschoolwheeze and childhood asthma, predicting the outcome of wheeze inpreschool children is, and is likely to remain, a mission impossible.

Conflicts of interest The author declares that he has no conflicts of interestin relation to this article.

Commissioned article; not externally peer reviewed; accepted 21st January 2014;online 19th February 2014© 2014 Primary Care Respiratory Society UK. All rights reservedhttp://dx.doi.org/10.4104/pcrj.2014.00010Prim Care Respir J 2014; 23(1): 10-11

References 1. Smyth A. Birth cohorts in childhood asthma: lessons and limitations. Am J Respir

Crit Care Med 2012;185:238-9. http://dx.doi.org/10.1164/rccm.201111-1952ED

2. Brand PL, Baraldi E, Bisgaard H, et al. Definition, assessment and treatment of

wheezing disorders in preschool children: an evidence-based approach. Eur Respir

J 2008;32:1096-1110. http://dx.doi.org/10.1183/09031936.00002108

3. Rossi GA, Cerasoli F, Cazzola M. Safety of inhaled corticosteroids: room for

improvement. Pulm Pharmacol Ther 2007;20:23-35.

http://dx.doi.org/10.1016/j.pupt.2005.10.008

4. Fouzas S, Brand PL. Predicting persistence of asthma in preschool wheezers: crystal

balls or muddy waters? Paediatr Respir Rev 2013;14:48-52.

http://dx.doi.org/10.1016/j.prrv.2012.08.004

5. Cane RS, Ranganathan SC, McKenzie SA. What do parents of wheezy children

understand by "wheeze"? Arch Dis Child 2000;82:327-32.

http://dx.doi.org/10.1136/adc.82.4.327

6. Lowe L, Murray CS, Martin L, et al. Reported versus confirmed wheeze and lung

function in early life. Arch Dis Child 2004;89:540-3.

http://dx.doi.org/10.1136/adc.2003.038539

7. Cano-Garcinuño A, Mora-Gandarillas I and the SLAM Study Group. Wheezing

phenotypes in young children: an historical cohort study. Prim Care Respir J

2014;23(1):60-66. http://dx.doi.org/10.4104/pcrj.2014.00008

8. Savenije OE, Granell R, Caudri D, et al. Comparison of childhood wheezing

phenotypes in 2 birth cohorts: ALSPAC and PIAMA. J Allergy Clin Immunol 2011;

127:1505-12. http://dx.doi.org/10.1016/j.jaci.2011.02.002

9. Mallol J, Garcia-Marcos L, Sole D, Brand P. International prevalence of recurrent

wheezing during the first year of life: variability, treatment patterns and use of

health resources. Thorax 2010;65:1004-09.

http://dx.doi.org/10.1136/thx.2009.115188

10. Pescatore AM, Dogaru CM, Duembgen L, et al. A simple asthma prediction tool for

preschool children with wheeze or cough. J Allergy Clin Immunol 2014;133:111-

18. http://dx.doi.org/10.1016/j.jaci.2013.06.002

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12PRIMARY CARE RESPIRATORY JOURNALwww.thepcrj.org

Editorials

COPD is a highly prevalent chronic disease which can cost acountry hundreds of millions of dollars per year. So it seemsappropriate for as much of the diagnosis and care of patientswith COPD to be managed by the most cost-effective health careproviders as possible whilst maintaining quality outcomes.1

The important study reported by Strong and colleagues2 in thisissue of the PCRJ examines a step forward in this process. In additionto the usual care system for patients with COPD, the city ofRotherham, England also has a specialist nurse-led respiratory carecentre called “Breathing Space”. This service is led by a respiratorynurse consultant and has a team of nursing, physiotherapy andoccupational therapy staff providing outpatient assessment, diagnosis,and treatment of COPD. The authors evaluated the accuracy of adiagnosis of COPD from over 1200 consecutive patients referred toBreathing Space from the 36 general practices in the city. Around halfof these patients were referred for pulmonary rehabilitation. Aboutone in five patients did not have airway obstruction on pre-bronchodilator spirometry testing, indicating that the primary careprovider's diagnosis of COPD was incorrect. There was pooragreement between the airflow obstruction grade recorded on thereferral and that based on spirometry. Patients referred by a practicenurse were more likely to have been correctly classified whencompared to patients referred from a general practitioner (GP). Asimilar study on the ability of practice nurses to perform spirometryand diagnose COPD correctly is underway in 36 GP offices in Sydney,Australia,3 and we look forward to seeing the outcomes.

The high rate of misclassification of the grade of airflowobstruction in primary care observed by Strong et al.2 is importantbecause the pharmacological treatment of COPD is based on thedegree of airway obstruction. It follows that a standardised process toperform and interpret spirometry is needed. The PLATINO study, apopulation-based survey conducted in five large Latin American cities,showed that more than half of smokers with severe airwayobstruction (FEV1 <50% predicted) had not been previouslydiagnosed.4 On the other hand, about two-thirds of the adults with aprior COPD diagnosis had normal spirometry (which is incompatible

with COPD). In our opinion, inaccurate diagnostic labeling of COPDnow represents an important health problem worldwide, not only inthe UK and Latin America.

Improved use of spirometry by primary care personnel, such astrained nurses, should be part of a strategy to improve COPDdiagnosis and management.5 However, it will be a challenge totransfer the assessment of patients at risk for COPD from secondaryor tertiary care centres to primary care facilities. This “transfer” shouldbe performed while ensuring quality control of spirometryperformance and interpretation, as well as symptom assessment,using clinical practice guidelines which are not influenced by industrysponsors.6 Besides the applicability of nurses’ standardised knowledgein terms of COPD diagnosis, multidisciplinary group participationwithin the practice is crucial. We can learn from the progress madeduring the past two decades in the management of another commonchronic disease, type 2 diabetes mellitus. Nowadays, most patientswith diabetes are successfully evaluated in primary care centresinstead of expensive and sophisticated tertiary level centres.

In terms of study limitations, details were not given regarding thetraining, certification, and duration of experience of the respiratorynurses working at Breathing Space,2 but these factors are importantand differ widely from place to place. The majority of older patientswith COPD have comorbid conditions (such as heart failure, obesity,anxiety, and depression), so the detection and treatment of thesecomorbid diseases is very important,7 but this is not described by thispaper. Furthermore, the appropriateness and the efficacy of thetreatments provided by Breathing Space for patients whose COPDwas confirmed were not reported. Although they are unable to curethe disease, current COPD treatments can reduce shortness of breath,improve exercise capacity and quality of life, and reduce the frequencyof acute exacerbations for some patients. Since smoking cessation isthe only action that will slow the rate of disease progression, moreenthusiastic and prolonged efforts should always be provided forcurrent smokers with COPD. The most important clinical outcomemeasures – i.e. quality of life and morbidity (especially expensiverespiratory-related hospitalisations), as measured by other studies8,9 –were not reported by this cross-sectional study, so we urge theinvestigators to consider these patients as a cohort and follow theseimportant outcomes over several years.

Conflicts of interest The authors declare that they have no conflicts ofinterest in relation to this article.

Commissioned article; not externally peer reviewed; accepted 11th February 2014;online 19th February 2014© 2014 Primary Care Respiratory Society UK. All rights reservedhttp://dx.doi.org/10.4104/pcrj.2014.00016Prim Care Respir J 2014; 23(1): 12-13

References 1. Nici L, ZuWallack R. American Thoracic Society subcommittee on integrated care of

the COPD patient. An official American Thoracic Society workshop report. Proc Am

Can nurses successfully diagnose and manage patients withCOPD?

*Paul Enright1, Elizabeth Halcomb2, Luis Torre-Bouscoulet3

1 Professor of Medicine (retired), The University of Arizona, Tucson,Arizona, USA

2 University of Wollongong, NSW, Australia 3 Instituto Nacional de Enfermedades Respiratorias (INER),

Mexico City, Mexico

*Correspondence: Professor Paul EnrightTel: +520 576 1030 E-mail: lungguy@gmail.com

See linked article by Strong et al. on pg 67

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Editorials

Thorac Soc 2011;9:9-18. http://dx.doi.org/10.1513/pats.201201-014ST

2. Strong M, Green A, Goyder E, et al. Accuracy of diagnosis and classification of

COPD in primary and specialist nurse-led respiratory care in Rotherham UK: a cross

sectional study. Prim Care Respir J 2014;23(1):67-73.

http://dx.doi.org/10.4104/pcrj.2014.00005

3. Bunker JM, Reddel HK, Dennis SM, et al. A pragmatic cluster randomized

controlled trial of early intervention for COPD by practice nurse-general practitioner

teams: study protocol. Implement Sci 2012;7:83.

http://dx.doi.org/10.1186/1748-5908-7-83

4. Tálamo C, de Oca MM, Halbert R, et al. for the PLATINO team. Diagnostic labeling

of COPD in five Latin American cities. Chest 2007;131(1):60-7.

http://dx.doi.org/10.1378/chest.06-1149

5. Fletcher MJ, Dahl BH. Expanding nurse practice in COPD: is it key to providing high

quality, effective and safe patient care? Prim Care Respir J 2013;22:230-3.

http://dx.doi.org/10.4104/pcrj.2013.00044

6. Bellamy D, Bouchard J, Henrichsen S, et al. International Primary Care Respiratory

Group (IPCRG) guidelines: management of chronic obstructive pulmonary disease

(COPD). Prim Care Respir J 2006;15:48-57.

http://dx.doi.org/10.1016/j.pcrj.2005.11.003

7. Lenferink A, Frith P, van der Valk P, et al. A self-management approach using self-

initiated action plans for symptoms with ongoing nurse support in patients with

chronic obstructive pulmonary disease (COPD) and comorbidities: the COPE-III

study protocol. Contemp Clin Trials 2013;36:81-9.

http://dx.doi.org/10.1016/j.cct.2013.06.003

8. Ingadottir TS, Jonsdottir H. Partnership-based nursing practice for people with

chronic obstructive pulmonary disease and their families: influences on health-

related quality of life and hospital admissions. J Clin Nurs 2010;19:2795-805.

http://dx.doi.org/10.1111/j.1365-2702.2010.03303.x

9. Wood-Baker R, Reid D, Robinson A, Walters EH. Clinical trial of community nurse

mentoring to improve self-management in patients with chronic obstructive

pulmonary disease. Int J Chron Obstruct Pulmon Dis 2012;7:407-13.

http://dx.doi.org/10.2147/COPD.S32220

Available online at http://www.thepcrj.org

For details on submission dates, how to get help, how to submit your abstract, and guidance onartwork together with notes for contributors, please log on to http://www.pcrs-uk.org/abstracts

Be a part of the Conference - Share your work with the PCRS-UKThe PCRS-UK is willing to offer support to those without previous experience of submitting posters.

*prizes available only to entrants who are submitting original work which has not previouslybeen published or presented at national/international meetings and conferences

The PCRS-UK is a registered charity (Charity Number: 1098117) and a company, registered in England and limited byguarantee (Company number 4298947). Registered offices: PCRS-UK, Unit 2 Warwick House, Kingsbury Road,Curdworth, Sutton Coldfield B76 9EE Telephone: +44 (0)1675 477600 Facsimile: +44 (0)121 336 1914

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Primary Care Respiratory Society UKNational Primary Care Respiratory Conference

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2. Sharing Best Practice – the power ofaudit and quality improvement projects

If you have been involved in a project which haschanged practice in primary care, why not submitan abstract describing your project and its

findings? This is an opportunity for you to showcaseyour work, share your experiences and discuss the outcomes ofyour work with colleagues. We are particularly keen to see theresults of local or national audits which have the potential toimprove outcomes for our patients in primary care.

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If you are involved with a research project on anyaspect of primary care respiratory medicine, this isyour opportunity to present your findings and get

valuable feedback from primary care-based clinical andacademic colleagues. For those new to research it looks great onyour CV and is a chance to meet other like-minded individuals.Previous feedback from both junior and experienced researchershas shown that the Original research abstract presentation sessions

at the conference are stimulating, enjoyable and useful.

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CALL FOR ABSTRACTS - PCRS-UK Clinical and Scientific Abstracts 2014

The annual PCRS-UK conference aims to showcase community-based respiratory research and innovative clinical/service developmentsthrough a series of abstract-based oral presentation sessions throughout the conference as well as a poster display in the exhibition area.

We are therefore inviting submission of abstracts for oral presentation in the research sessions, andposter submissions for display in the exhibition area, throughout the 2014 PCRS-UK conference.

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Figure 1 to accompany Editorial by Soriano and Román-Rodríguez

Andres Iniesta's winning goal against Netherlands in the July 11th, 2010 World Cup Final. [as per www.google.comphoto search on February 6, 2014.]

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