More than 400 participants from 29 countries attended the IPCRG’s 3rd World Conference and were rewarded with lots of Inspiration, with presentations of much Practical information for Clinical practice, new Research results and even introduction to a new term: GyPSIes, which stands for General Practitioners with Special Interest (GPwSI). We summarise some of the highlights for you here.

• Ethical issues
• Lung function testing
• Allergy testing
• One airway, one disease
• New diagnostic tools in asthma
• Follow up in asthma
• New insights in mediator functions
• Allergy and prevention
• Paper spacers in Sri Lanka
• Withdrawal of ICS in COPD
• COPD and prevention?
• Epidemiology of COPD
• Diagnosis of COPD
• Treatment opportunities in COPD
• Follow up in COPD
• Important role for community workers
• Smoking cessation

Douglas Fleming from the UK presented some ethical issues of treatment in a global view. A lowered life expectancy at birth is always politically influenced, he stated, with Zimbabwe as an example. Pandemic flu will probably arise from South East Asia and is carefully being observed by those in the West, who are hoping to be able to produce a vaccine as soon as possible. But will the vaccine be available in sufficient amounts for the South East Asians as well? Or will the West satisfy their own needs before exporting vaccine? As long as there are regional inequalities there will be ethical dilemmas. Many patients have little or no access to diagnostic and therapeutic instruments, but this does not mean that nothing can be done. Fleming also pleaded for openness about resources. How reliable are they? How are we to interpret research results properly? And what about a new phenomenon, the patient’s record? Do we record what we see, hear and smell, or what we want to? Do we look for signs and symptoms that suit the diagnosis we have in mind (tunnel vision)?

Siren Nicolaisen and Elise Austegard both from Norway, presented an overview of lung function testing. It is important to avoid testing spirometry shortly after smoking, eating a big meal, drinking alcohol or after a major exertion. Curves will not be representative and reproducible and therefore not reliable. To get the best results, in keeping with the ERS recommendations, utilising the best of three curves, which should meet reproduceability criteria (less than 5%). Flow volume loop, FVC, FEV1 and their ratio are the most measured values; others suggested carefully that FEV6 would probably be a more representative value in weaker and/or dyspnoeic patients. (See the October 2006 issue of the Primary Care Respiratory Journal for papers and Editorials on this subject: http://www.sciencedirect.com/science/journal/14714418)

Spirometry needs training and training maintenance: two times four hours (a year) results in 84% acceptable curves.

Samantha Walker from the UK led us to the insight that allergy testing is only useful if an avoidable trigger is presumed. As airborne allergens are generally not avoidable she proposed not to test the hay fevers, as patients themselves generally know best to which pollen they are allergic! Avoidable triggers are insects, food and drugs, e.g. penicillin. It is important to diagnose those allergies and where possible to desensitize the patient. Accurate allergy diagnosis depends on the concordance (or lack of it) between the patient’s history and the results of an objective measurement of allergen-specific IgE antibodies. Skin prick tests and blood tests are available to identify or exclude an IgE-mediated mechanism in patients with allergic symptoms. The magnitude of the response does not necessarily correlate with disease severity. There is a relatively good correlation between the two tests, so the choice of test is likely to be based on the nature of symptoms, safety, availability, and cost and operator expertise in the interpretation of results.

Professor David Price from the UK spoke about rhinitis and asthma. (View presentation). He pointed out that both could be symptoms of the same disease: one airway, one disease. The WHO and others have recently described this as the so-called "One-Airway Concept". Although rhinitis and asthma are both common diseases, they coexist more frequently than would be expected by chance with epidemiological data. The vast majority of asthma patients also suffer from allergic rhinitis and up to 40% of rhinitis patients also suffer from asthma. Both diseases share similar triggers and similar pathophysiology, characterised by almost identical inflammatory cell infiltrates. The evidence suggests a central mechanism behind the link with eosinophil precursors emanating from the bone marrow in response to triggers migrating not only to the site of stimulation, such as the nasal mucosa, but also to other sites within the one airway, including the lower respiratory tract.

Three areas of research suggest there is a real importance clinically in the "One-Airway Concept". First it could be possible to interfere in the development of asthma in patients with rhinitis, secondly the severity of rhinitis appears to be a risk factor for poor asthma control and finally common anti-inflammatory therapy may improve outcomes for both. New international guidelines for primary care management of respiratory disease therefore attract special attention to rhinitis. Not only should rhinitis be looked for in patients with asthma and vice versa, but also since rhinitis is a risk factor for poor asthma control, it should be looked for in uncontrolled asthma and most importantly to achieve good asthma control it is necessary to treat rhinitis adequately in patients with asthma. "If you don’t control the nose, you can’t control the lungs" another speaker noted.

Dr. Mike Thomas from the UK, considered specific testing tools in asthma, and concluded that there is room for improvement in asthma control, as most asthma patients are seen in general practice in the first line, and many of them are badly controlled. (View presentation). We often diagnose and assess asthma from symptoms and lung function, but both are a poor guide to asthma severity. Psychological and sociological symptoms correlate poorly with the severity of asthma. Bronchial hyperreactivity (BHR) can be used to assess airway inflammation and asthma severity, but this test is not often measured in primary care.

Studies based in secondary care settings have suggested that the diagnosis and management of asthma may be improved by using objective assessments of BHR and inflammation, i.e. quantification of differential eosinophil counts in induced sputum samples and estimation of exhaled nitric oxide (eNO). eNO is a simple, quick, sensitive and cheap (5 Euro) index for asthma severity in non-smokers, and can help to tailor the dose of inhaled corticosteroids without losing asthma control.

Bjørn Ställberg from Sweden stated that follow up in asthma management is a shared care for first and second liners. (View presentation). Nurse practitioners play an important role in this and although asthma is often mentioned (and managed) together with COPD, Ställberg advised us to differentiate between the two diseases in follow up and management. The list of comorbidities associated with smoking encompass 92 diseases, and 50% of the smokers will die from one of them, which makes COPD a different disease from asthma. Besides, airflow limitation in COPD is less reversible than in asthma, COPD is often asymptomatic until its late stages and COPD is a slowly progressing disease. These factors are clearly different from those in asthma and therefore require a different approach.

Dr Ola Storrø from Norway gave an excellent overview of mechanisms and mediators in the allergic response. New knowledge of T regulatory cells as key regulators of immunologic processes in peripheral tolerance to allergens has opened an important era in the prevention and treatment of allergic diseases. (View presentation). This will have implications for drug development and allergen-specific immunotherapy in the near future. Dr Storrø brought up for discussion the interesting idea that allergy may be a tolerance deficiency syndrome.

T regulatory cells directly or indirectly suppress and inhibit effector cells of allergic inflammation (mast cells, basophiles, and eosinophils). The increased levels of IL-10 and TGF-beta produced by T regulatory cells, can suppress IgE production while increasing the production of the noninflammatory antibody isotypes IgG4 and IgA. A better understanding of these and other mediators of allergic inflammation will possibly lead to potential cures for allergic diseases.

Nicholas J. Glasgow from Australia tried to convince the audience that there is a role for prevention in allergy. (View presentation). Allergy according to World Allergy Organization definitions is a hypersensitivity reaction initiated by immunological mechanisms. Allergy can be antibody- or cell-mediated. In the majority of cases the antibody typically responsible for an allergic reaction belongs to the IgE isotype and these individuals may be referred to as suffering from an IgE-mediated allergy.

Atopy is a clinical definition of an IgE antibody high responder. Primary prevention is the prevention of immunological sensitisation. Secondary prevention is the prevention of the expression of symptoms of atopic disease following sensitisation. Using Medline Dr. Glasgow and co-workers decided that a few primary prevention activities are clearly supported with good evidence, including avoidance of smoking and exposure to environmental tobacco smoke during pregnancy and early childhood, breastfeeding and for young children at high risk, reduced exposure to aero allergens. Regarding secondary prevention treatment of atopic eczema and allergic rhinoconjunctivitis may prevent onset of allergic disease. So both primary and secondary prevention help to reduce the incidence and severity of atopic diseases, or in a nutshell: smoking kills and breastfeeding helps, according to Dr. Glasgow.

Spacer devices coupled to inhalers are a major breakthrough in the treatment of asthma, but all standard spacers are expensive and out of reach for the majority of Sri Lankan patients. Therefore Dr. Senath Samaranyake from Sri Lanka tried to assess the clinical efficacy of drug delivery using paper spacers and presented a discussion poster on this subject. 134 patients with an acute episode of wheezing were examined (peak flow rate –PEFR- before, after placebo and after salbutamol inhalation). An increase of PEFR of 20% from the basal value was regarded as a good response. Paper devices of different sizes and a standard volumatic spacer showed equal efficacy. The cost of a paper spacer device is negligible compared to that of the volumatic spacer and therefore the use of paper spacers in Sri Lankan family practice will make inhaled therapy much cheaper without decreasing the effectiveness of drug delivery.

Daryl Freeman from the UK stated that the most common killer in COPD is a heart disease. COPD does not only affect the airways, but is a systemic inflammatory disease. She presented two studies where the use of inhaled corticosteroids (ICS) was stopped in COPD patients. Colleagues from Norway in the audience told earlier that the Norwegian government is considering stopping reimbursement of ICS for COPD patients.

In the first study more problems arose than expected, including lung function deterioration and an increase in exacerbations. In the second study 40% of patients got in trouble within 4 months after freezing the use of ICS. According to several standards 80% of COPD patients could do without steroids, however Dr. Onno van Schayk from the Netherlands calculated that 50% of COPD patients can do without ICS. In daily life 80% of COPD patients use ICS.

An interesting question is if case-finding and early intervention prevents development into moderate to severe COPD. Dr. Georgio Stratelis from Sweden (view presentation) discussed the pro and Dr. Patrick White from UK (view presentation) the con arguments. Pro arguments include the fact that the disease is highly under diagnosed (75% of all patients is not known to their doctors and themselves). Reasons for the patients delay are a low knowledge of the disease and adaptation, while the doctor’s delay seems due to the fact that the doctor is busy or not interested or that symptoms are not reported. Many studies have expounded the virtues of early treatment of COPD. According to Dr. White this apparently reasonable position is however, a complex challenge. While smoking cessation is the key to early intervention in COPD, there is no evidence that early diagnosis of COPD improves the take up of smoking cessation strategies.  Drugs are largely ineffective in early stages of the disease and the patient with low or no symptoms will not be very motivated to seek medical treatment. A more important argument is that case-finding and early intervention in mild disease steals healthcare from people with more severe disease and diverts resources from what should be the main focus of the health carer’s attention.

Niels Chavannes from the Netherlands gave an overview of the epidemiology of COPD. Figures from the nineties show that worldwide die 3 million people every year due to the consequences of smoking, which is one every ten seconds! By now estimates are that the global death toll has risen to 4.8 million every year, that is one in every six seconds! Half of COPD deaths now occur in China where biomass fuels are an important threat in addition to tobacco consumption. Especially women and children are at risk of indoor biomass fuel exposure.

International goals to be achieved are: guidelines, simple spirometry, cheap non-pharmaceutical therapy, education and smoking cessation, reducing biomass exposure, with special attention to developing countries. At the same time awareness rises that COPD is a complex disease, which cannot be tackled by single interventions. The idea is that integrated disease management, including a carefully tailored exacerbation action plan based on close cooperation between patient and caregiver team can possibly generate better outcomes.

Dr. Miguel Roman Rodriguez from Spain said that COPD is considered a systemic inflammatory disease. (View presentation). There is an estimated under diagnosis of 71-78%. Only a fraction of all smokers, 20-25%, will develop COPD. Diagnosis is difficult. Usually there are no symptoms in early stages. COPD is an auto inflicted disease: patients feel guilty about their smoking habits and don’t consult till they are suffering from great dyspnoea in advanced stages. Doctors delay because of assumed therapeutic nihilism, lack of symptoms and lack of simple diagnostic tools. Office spirometry is the best test for early diagnosis in poor symptomatic stages, and spirometry facilities should be available in every primary care practice as recommended by international guidelines. Half of all primary care practices in Spain have spirometer facilities.

There is confusion because of different terms: chronic bronchitis and emphysema are used when COPD is meant. There could be confusion with the diagnosis asthma. Half of all COPD patients have been diagnosed as asthma patients before. Another difficulty in diagnosis is the combined asthma – COPD patient.

Some people think that COPD is a geriatric disease, but they are wrong. In the age group 20-40 years 3.6% have COPD and 11% are at risk. The use of inhaled corticosteroids (ICS) is disputed, but according to Dr. Rodriguez, ICS reduce mortality in COPD with 20%.

We all know that COPD is a multifactorial disease, and many of us regard COPD as a hopeless or forgotten disease. Almost every smoker is aware of the risk of having lung cancer one day, less is aware of the risk of COPD. In the year 2000 there were 340.000 lung cancer patients in USA and 13.000.000 patients with diagnosed COPD, Dr. Jim Reid from New Zealand told the audience. (View presentation) These facts should be an enormous challenge to us all. BTS guidelines set out five goals for COPD management: early and accurate diagnosis, best control of symptoms, prevention of deterioration, prevention of complications and improved quality of life. The opportunity for treatment depends on early diagnosis, dealing with causative factors and initiating appropriate treatment for the stage of the disease process.

Smoking cessation is the single most effective - and cost effective – intervention to reduce the risk of developing COPD and stop its progression. Although only 25-30% of all smokers will develop COPD, 100% of them have symptoms of COPD, according to Dr. Reid. Cornerstone of treatment is the use of broncho dilators. There is a choice between short acting and long acting beta agonists, anticholinergics and a combination of them, and theophylline. Inhaled corticosteroids (ICS) are not effective in neutrophil induced inflammations, but have been shown to reduce the exacerbation rate in moderate to severe COPD (stage 3 and 4). Dr. Reid mentioned that the safety of long acting beta agonists is not proven with COPD and that theophylline is a third line treatment. Another treatment opportunity is rehabilitation, which includes not only exercise (walking), but also nutrition and education. (long term) Oxygen, lung reduction surgery and lung transplant are opportunities in more advanced cases. In case of an exacerbation one uses antibiotics, regional bronchodilators (nebulisator) and oral glucocorticosteroids. Most promising are the fosfodiesterase inhibitors. Vaccination against influenza and pneumococcen seems to be highly effective in preventing exacerbations, according to Dr. Reid.

National and international guidelines recommend that people with COPD should be reviewed regularly. The primary aims are to monitor disease progress, identify complications, and assess the impact on symptoms and quality of life. Dr. Hilary Pinnock from UK pointed out that NHS guidelines advise to measure lung function at least once a year, while GOAL guidelines say not more than once a year. Dr. Pinnock would like to know what IPCRG’s coming guidelines will advise. She stated that the use of dyspnoea scores may correlate better with functional impairment of lung function than spirometry.

A valuable index may be the BODE-index, in which B stands for Body Mass Index, O for the rate of airflow Obstruction, D for Dyspnoea, and E for exercise capacity, i.e. the well known 6 minutes walking test. More useful tools can be found at www.pulmonaryrehab.com.au.

In more advanced stages of COPD patients will benefit from a multidisciplinary approach, with attention for different needs. Although models of care will vary with different healthcare systems, respiratory nurse specialists, physiotherapists, occupational therapists and dieticians may contribute, while social help and palliative care should be offered to those who need it. When is the moment to think about offering palliative care? Deciding the right moment for offering palliative care may be difficult for a dedicated healthcare worker who accompanies a patient during a long period. Dr. Pinnock asks herself if she would be surprised if her patient would die within the next twelve months. If the answer is "no", it might be a good moment to consider and discuss the start of palliative care.

Interesting moments arose during the interactive case discussions in plenary sessions which took place twice a day. There were heavy and sometimes witty debates about smoking cessation strategies, the role of inhaled corticosteroids in COPD, the (over)use of antibiotics in lower respiratory infections, the role of combination therapy in mild to moderate asthma and others. Without exception all discussions were vivid and instructive as so many views and opinions passed, which in many cases clarified different international possibilities and barriers.

Professor Chris van Weel from the Netherlands considered COPD care and directed us from the disease to the patient. (View presentation). "Our patients need GP’s, not specialists", he concluded at the end of his presentation.

COPD is the most common chronic respiratory condition in communities around the world and it is predicted that its prevalence will increase in the coming decades. Epidemiological data from general practice stress that on average quality of life of most patients with COPD is high and the exacerbation rate low, particularly in those in GOLD stage 1 and 2, the stages of most patients with COPD in primary care. However, it remains unclear to what extent individual patients show true disease progression, and co-morbidity is a rule rather than an exception. This makes it difficulties in applying disease-specific guidelines to patients who suffer from multiple morbidities and who show an unpredictable progression state. That’s why research in primary care should be directed more at patients and less at the disease. The understanding of co-morbidity and its management implications, the natural course of the disease, persistent smoking and other life style factors in subjects with low socio-economical perspectives, implies a substantial shift from a reliance on drugs and secondary care towards care in the community setting, according to Van Weel.

Stopping smoking is difficult, only 5% of those who undertake an effort will succeed on their own. Medication doubles the success rate, but only in the beginning. Several speakers presented the problem from different views, and according to Dr. Anders Østrem, this subject should be the most important of the whole conference. What other free available product kills half of its dedicated users? A smoker at risk (with limited air flow) is more motivated to give up smoking than a non risk smoker. Who is at risk? Screening is too complicated, but case finding may be an idea. Prof. Onno van Schayck (Article) from the Netherlands uses a simple COPD questionnaire of 8 questions. If the patient is over 40 years of age and shows the most predictive symptom –coughing-, and is at risk for COPD according to the questionnaire, spirometry is offered. After a myocardial infarct 9 out of 10 patients decide to stop smoking, but how can we motivate our patients before their MI? Dr. Svein Hoegh Henrichsen from Norway (Article) advised to use the 5 A programme: (1) Asking every patient about tobacco use, (2) Advising all smokers to quit, (3) Assessing smokers’ willingness to make a quit-attempt, (4) Assisting smokers with treatment and referrals, and (5) Arranging follow-up contacts. Smoking cessation is not a popular subject in everyday practice, but simple asking after and showing interest in patient’s smoking habits can make a difference for some. And if they relapse, there could be a new attempt. Relapsing is common among quitters, so encourage them to make a new attempt. Only few succeed the very first time!

A good question might be: what is your favourite cigarette of the day? And then try to break that behaviour.

Nicotine seems to be a strongly addictive substance, comparable to heroin. It arrives in the brain 7 seconds after inhaling cigarette smoke. There it makes you feel pleasant and euphoric by stimulating acetylcholine receptors on dopamine neurons, to release their neurotransmitters. The more often you smoke the more nicotine acetylcholine receptors you create, which make you quickly addicted to nicotine. Therefore, the longer you smoke, the more difficult it is to quit. Not any nicotine replacement therapy can mimic the speed of nicotine action to the brain after inhalation (7 seconds); therefore its results are limited. Tobacco addiction is not equal to nicotine addiction. It takes 3-4 weeks to overcome the withdrawal symptoms physically, 3-4 months to master them psychologically, and 3-4 years before you get the idea that you never start smoking again.

Dr. Janneke Kaper from the Netherlands gave an overview of medical treatment for smoking cessation. Since using smoking cessation treatment seems to be highly cost-effective even in smokers with COPD, the use of these treatments should be promoted, she stated. One way to increase its use may be to offer reimbursement. In the Netherlands there is no reimbursement for this treatment. According to Dr. Kaper this has to do with your thoughts about smoking. Is smoking an addiction (medical view) or a lifestyle (economic view)? The Minister of Health being a doctor promotes reimbursement, while the businessman does not. Dr. Kaper calculated that if society is willing to pay 18000 Euro for a Quality Adjusted Life Year, the probability that reimbursement would be cost-effective was 95%.

Nortriptyline and bupropion are the two medicaments of which there are enough randomized placebo controlled trials (RCT) and are proven effective smoking cessation interventions. Three companies worldwide are preparing nicotine vaccines. These create antibodies that form a complex with nicotine that cannot enter the blood brain barrier. Vaccines are proven safe, but more evidence is needed to decide if they help at cessation.

Hetty van Dijk
1 September 2006