Showing posts with label COPD. Show all posts
Showing posts with label COPD. Show all posts

Thursday, March 5, 2009

Managing chronic obstructive pulmonary disease in primary care

Medical Tribune December 2008 P14 & 15

Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide, affecting some 210 million people. It is expected to become the third leading cause of death by 2030, according to WHO estimates.

COPD is characterized by airflow limitation, which unlike asthma, is not fully reversible. The airflow limitation is progressive and is associated with an abnormal inflammatory response to noxious particles or gases. It is a preventable disease, primarily caused by tobacco smoke. In some countries, where there is exposure to indoor air pollution, the use of biomass fuels for cooking and heating can cause COPD.

The disease has a chronic progressive course. As lung function declines the patient’s symptoms worsen and they become increasingly dependent on the healthcare system for medical care, which may include hospitalization. Although not curable, treatment is available which helps relieve symptoms and improve quality of life.

GPs can play an important role in the management of COPD in the community: in addition to providing treatment to stable patients, they can also help to educate patients and identify those who are at risk and should be screened.

Diagnosis

A diagnosis of COPD should be considered in any patient who has breathlessness, chronic cough, sputum production and a history of smoking. COPD can sometimes go unrecognized as the symptoms are commonly attributed to smoking and ignored.

Patients often seek medical attention for breathlessness. This may occur only on exertion or strenuous activity in patients with mild disease, but as the condition progresses and lung function deteriorates the breathlessness can become persistent and can be disabling and frustrating to the patient. Cough is a common symptom in COPD but its significance may not be appreciated by smokers, who may consider it to be a consequence of the habit and not seek further attention or assessment. The amount of sputum brought up is variable, and might be purulent during an infective exacerbation.

The diagnosis of COPD should be confirmed by spirometry. This is presently the gold standard for establishing the diagnosis, providing reproducible and objective results. The presence of a post-bronchodilator Forced Expiratory Volume (FEV)1 / Forced Vital Capacity (FVC) less than 70 percent, and an FEV1 above 80 percent of predicted values confirms the presence of airflow limitation that is not fully reversible. Spirometry also permits COPD to be classified into four stages of severity: stage 1, mild; stage 2, moderate; stage 3, severe, and stage 4, very severe, according to the FEV1 predicted.

Spirometry is not typically available in primary care practices but can be ordered at most hospitals and some polyclinics. GPs can facilitate an early diagnosis of COPD by identifying patients who are at risk and referring them for further testing.

Screening studies have shown that many patients who have been diagnosed with COPD are unaware of it, even when they have advanced disease. Subjects aged over 40 who have any smoking history and breathlessness, chronic cough and sputum production, are at risk of COPD and should be identified and encouraged to undergo spirometry. This represents
an opportunity for GPs to diagnose the disease and initiate treatment which may slow its progression.

Practice Guidelines

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) provides helpful, informative guidelines on the diagnosis, management and prevention of COPD. These were most recently updated in 2007, and are easily accessible from the GOLD website. International
guidelines are also available from a range of other sources including the American Thoracic
Society, the European Respiratory Society and the National Institute for Health and Clinical Excellence (NICE), UK.

Locally, the Ministry of Health, Singapore, published COPD guidelines in 2006.

Treatment

The goals of management in COPD are the relief of symptoms, prevention of disease progression, improvement of exercise tolerance, improvement of health status, prevention
and treatment of complications, prevention and treatment of exacerbations, and reduction of
mortality.

All patients with COPD should be educated on the disease. This can be time-consuming in the busy practice schedule of a GP but a good understanding of the disease helps the patient to better participate in the management of his disease. Patients should be advised to stop smoking and provided with the necessary support to facilitate this. Education should also address coping skills and the use of medications and inhalers.

The majority of patients encountered by GPs will have mild (FEV1 > 80 percent predicted) or
moderate (FEV1 50 – 80 percent predicted) COPD and are usually in a stable condition. Bronchodilators are central to the management of symptomatic COPD. Many patients seek treatment because of breathlessness which restricts their activities and can be disabling. A short-acting bronchodilator – either a beta2-agonist (e.g. salbutamol) or an anticholinergic (e.g. ipratropium) – can be prescribed on an as-needed basis for relief of symptoms or on a
regular basis to prevent or reduce symptoms. The preferred route of delivery is by inhaler.

For persistent symptoms, a combination inhaler containing both a beta2-agonist and an anticholinergic can be used. If patients are still symptomatic, regular treatment with a long-acting bronchodilator is more effective and convenient than the short-acting bronchodilators. Tiotropium is a long acting anticholinergic agent which was shown in the recently-published Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) study to improve lung function, reduce the risk of exacerbations and hospitalization and improve quality of life. [N Engl J Med 2008 Oct 9;359(15):1543-54] Two recent publications (a meta-analysis and a nested case-control study) suggested an increased risk of cardiovascular events in patients using inhaled anticholinergic drugs but in the UPLIFT study there was a reduction of cardiac adverse events associated with tiotropium. [JAMA 2008 Sep 24;300(12):1439-50; Ann Intern Med 2008 Sep 16;149(6):380-90]

Inhaled corticosteroids are indicated in patients with severe and very severe COPD with an FEV1 ≤50 percent of predicted, and at least 2 exacerbations in the preceding 12 months. An inhaled corticosteroid combined with a long-acting beta2-agonist is more effective than the individual components. The Towards a Revolution in COPD Health (TORCH) study, published in 2007, showed that a combination regimen of salmeterol 50 mcg and fluticasone propionate 500 mcg twice daily reduced the rate of exacerbations and improved lung function and health
status. Patients taking fluticasone were also noted to have a higher incidence of pneumonia. [N Engl J Med 2007 Feb 22;356(8):775-89]

The long-term use of oral corticosteroids should be avoided as it is associated with unwanted adverse effects. The widespread use of mucolytic agents and regular use of antitussives is not recommended.

Exacerbations are defined as a sustained worsening of the patient’s symptoms from his usual stable state which is beyond the usual day-to-day variation and is acute in onset. The common symptoms are a worsening of breathlessness, cough, increased sputum production and a change in sputum color. The change of symptoms usually necessitates a change in medication,
comprising an increase in the frequency of bronchodilators, a course of antibiotics and prednisolone for a week. Mild exacerbations can usually be treated by the GP but patients who are very breathless, unable to cope at home and in poor general condition should be referred to the hospital for management.

Exacerbations are more common in patients with advanced disease, and are a major cause of
morbidity and mortality in COPD. The use of inhaled corticosteroids (alone or in combination with a long-acting beta2-agonist) and long-acting anticholinergics, as well as influenza and pneumococcal vaccination, can reduce the incidence of exacerbations. Patients should also be taught to recognize the development of an exacerbation so that immediate measures can be
taken to control it.

COPD patients should be encouraged to participate in physical activity. Many of those with breathlessness are often apprehensive to exercise for fear of worsening the dyspnea, owing to dynamic hyperinflation of the lungs. This can be overcome with the regular use of bronchodilators which help empty the lungs and improve effort tolerance. Deconditioning will occur if they remain sedentary and passive, resulting in muscle atrophy and weakness. Patients may also be referred to the hospital for pulmonary rehabilitation programs where an exercise regime tailored to the patient can be developed to help improve their exercise capacity and their ability to cope.

Disease management tools

Singapore’s National Healthcare Group Integrated Chronic Obstructive Pulmonary Disease
(NICE) program is a hospital-based initiative aimed at reducing hospitalization and readmissions from COPD, reducing emergency room visits and improving patient quality
of life. Team members include respiratory physicians, case managers and physiotherapists. The
physicians focus on the medical aspects of care, while dedicated case managers provide a more holistic approach by helping to educate patients and encouraging them to make lifestyle changes. Subsidized medications are also available through the program. There are currently over 500 COPD patients in the program.

At present the NICE program is solely hospital-based but this represents just an early step in a continuing journey to engage primary healthcare. In the long term we hope to share the ongoing management of our patients with the GPs and polyclinics, such that care during stable periods can be administered in the community with the hospitals on standby in the event of acute exacerbations. As well as facilitating our processes of care we hope that implementing this vision will improve awareness of COPD in the community and help primary care
practitioners to become more confident with handling the disease.

Conclusion

GPs and primary healthcare doctors play a major role in the management of COPD in the community and have a real opportunity to make an impact in the management of the disease. Smokers can be identified and advised on smoking cessation in order to prevent the development of COPD, while other high-risk patients can be sent for spirometry in order to
diagnose the condition. Patients with established COPD can be educated on the disease and the
effective treatments for symptom control. GPs can work in partnership with hospital physicians to help improve the framework of care for COPD patients in the community.


Online Resources:

The Global Initiative for Chronic Obstructive Lung Disease:
http://www.goldcopd.com/

The American Thoracic Society COPD guidelines:
www.thoracic.org/sections/copd/

The European Respiratory Society COPD guidelines:
www.ersnet.org/ers/default.aspx?id=1418

The National Institute for Health and Clinical Excellence, UK, COPD guidelines:
www.nice.org.uk/guidance/CG12

Wednesday, February 18, 2009

UPLIFT trial reassures on tiotropium safety

Medical Tribune November 2008 P16
David Brill

Doctors can be reassured about prescribing inhaled tiotropium as a treatment for chronic obstructive pulmonary disease (COPD), one of Singapore’s leading respiratory experts has advised in light of a recent trial publication.

The Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) study found that tiotropium was safe and significantly reduced the risk of cardiac adverse events among patients with moderate to very severe COPD.

The safety of inhaled anticholinergics had been called into question following the publication of two separate studies in September which linked the class of drugs to an increased risk of cardiovascular mortality.

One of the papers – a meta-analysis published in the Journal of the American Medical Association (JAMA) – reported a 58 percent increase in the risk of cardiovascular death, myocardial infarction or stroke among COPD patients taking either tiotropium or ipratropium. [2008 Sep 24;300(12):1439-50]

The US Food and Drug Administration (FDA) is conducting a thorough review of the findings from UPLIFT and expects to receive the full data set in November. However, the complete analysis could take several months, according to a statement on the FDA website.

The 4-year UPLIFT study, published in The New England Journal of Medicine, involved 5,993 patients from 37 countries who were randomized to tiotropium (18 μg once daily) or placebo. [2008 Oct 9;359(15):1543-54]

Dr. Ong Kian Chung, president of the Singapore COPD Association, said that he was happy with the safety data from UPLIFT and would continue to prescribe tiotropium as normal.

“I’m personally not too convinced that there is any significant complication from using these medications,” he said.

“The data from the meta-analysis isn’t enough to deny the patient the effectiveness of a long-acting anticholinergic. I think it’s more likely that it is a statistical fluke than a truly increased risk,” said Ong, who is currently a private practitioner at Mount Elizabeth Medical Centre, and was a co-investigator for the UPLIFT trial.

Patients in UPLIFT were allowed to continue their usual respiratory care with the exception of other inhaled anticholinergics, such as ipratropium, a shorter-acting formulation than the study
drug tiotropium. The use of these drugs was permitted, however, in the event of a serious exacerbation of COPD.

Dr. Sonal Singh, lead authorof the JAMA meta-analysis, questioned this aspect of the UPLIFT design and said that the trial does not invalidate the findings of the meta-analysis since the usage of ipratropium for exacerbations has not been reported.

“There might be differences in the risk between the long-acting and the short-acting, but UPLIFT is not going to answer that question because it was not designed that way,” he said.

“In one arm you have the long-acting and in the other arm you have people using the short-acting, so it’s not a valid comparison,” he said, adding that the meta-analysis demonstrated a higher cardiovascular risk with short-acting ipratropium than with long-acting tiotropium (risk ratios 1.70 and 1.43, respectively).

The meta-analysis incorporated 17 trials involving 14,783 patients.

A second paper, a nested case-control study including 32,130 cases and 320,501 controls, found an odds ratio of 1.34 for cardiovascular death associated with ipratropium. [Ann Intern Med 2008 Sep 16;149(6):380-90]

Tiotropium in UPLIFT was delivered with the HandiHaler inhalation device manufactured by Boehringer Ingelheim, which co-sponsored the trial with Pfizer.

Dr. Iylen Benedict, regional medical affairs director for Boehringer Ingelheim, said that the study by Singh et al. is methodologically flawed and pointed out that the majority of the evidence on ipratropium comes from a single study, the Lung Health Study. [Am J Respir Crit Care Med 2002;166(3):333-9]

“In this study, most of the cardiovascular deaths occurred among patients who were not using their medication,” she said.

“Other limitations [of the metaanalysis] include the inability to adjust for treatment duration and accounting for patients who discontinue the trial early, apparent double-counting of trials and combining placebo and active comparator drugs in the control group.”

Benedict also reiterated that the use of other anticholinergics such as ipratropium was not allowed in UPLIFT, and that the decision to allow any intervention in the face of a life-threatening exacerbation, as deemed necessary by a physician, was an ethical position.

She added that there are currently no plans for a trial looking specifically at cardiovascular outcomes with tiotropium, but confirmed that the full UPLIFT data will be provided to the FDA for the safety analysis.

UPLIFT did not reach its primary endpoint of significantly reducing the decline in forced expiratory volume 1, but did demonstrate significant improvements in lung function, exacerbations and quality of life with tiotropium therapy.

The trial included patients from seven Asian countries, including Singapore, Hong Kong, Malaysia and the Philippines. The results were first presented at the annual meeting of the European Respiratory Society, held recently in Berlin, Germany.