CIPLADOC - Publications - Tiova Scope - Issue 3

Publications

Tiova Scope - Issue - 3

GOLD 2003 Recommends New Treatment in COPD

The latest international guidelines published by Global Initiative for COPD (GOLD) now include tiotropium alongside with long-acting bronchodilators as first-line maintenance therapy for the management of COPD. Tiotropium is the only new compound to be included in the first guidelines update.

Top

This recognition of tiotropium as a first line maintenance therapy reflects the drugs efficacy in treating a wide range of patients with COPD. With appropriate diagnosis and treatment a patients quality of life can be significantly improved. Now there is an alternative therapy for those COPD patients who need an effective long term treatment option



"Within the GOLD treatment model tiotropium is recommended as a first-line maintenance treatment for COPD for all stages of disease severity where maintenance treatment is appropriate." GOLD 2003	"Changing the framework of treatment for COPD, and emphasising the fact that COPD patients can live a fruitful life is vital. Then for all of them, the future is bright. " - Dr. B. Celli,

Summary of New Recommendations

Between June 2000 and March 2003, 36 reviewed papers were identified to have an impact on the GOLD report of 2001. These included modifications, additions, replacements and some new concepts.

The major modifications to the management section included:

Position of long-acting and short-acting bronchodilators, including the introduction of the new long-acting anticholinergic, tiotropium

Position of inhaled glucocorticosteroids and combination of inhaled long-acting b2 agonists/ glucocorticosteroids

Evidence related to the length of pulmonary rehabilitation programs

Home vs. hospital care for COPD exacerbations.

Classification of severity

For academic reasons, the papers recommend a simple classification of disease severity into four stages and also at risk stage:

All values are post bronchodilator reversibility

Managing stable COPD

The overall approach to managing stable COPD should be characterised by a step-wise increase in treatment, depending on the severity of the disease. The step-down approach used in the chronic treatment of asthma cannot apply to COPD since COPD is usually stable and very often progressive. Management must include the following components:

a. Health education
Education plays an important role in improving skills, ability to cope with illness and overall state of health. It helps to accomplish certain goals, like smoking cessation.

b. Pharmacotherapy
Helps to control symptoms and/or complications.

c. Bronchodilator medications
These are central to symptomatic management of COPD. Given on 'as-needed' or 'regular' basis to prevent or reduce symptoms.

d. Long-acting bronchodilators
Compared to short-acting bronchodilators, regular treatment with long-acting versions (including tiotropium) is more effective and convenient.

e. Inhaled glucocorticosteroids
Addition of inhaled glucocorticosteroids to the regular regimen is appropriate for symptomatic COPD patients with an FEV1 < 50% predicted (in Stage III: severe COPD and Stage IV: very severe COPD) and repeated exacerbations.

f. Systemic glucocorticosteroids
It is best to avoid chronic treatment with systemic glucocorticosteroids on account of the unfavourable benefit-to-risk ratio.

g. Exercise programs
All COPD patients benefit from exercise-training programs, improving with respect to exercise tolerance as well as symptoms of dyspnoea and fatigue.

h. Oxygen administration
Long-term administration of oxygen (for more than 15 hours a day) to patients with chronic respiratory failure has been shown to increase survival.

Rehabilitation

The principal goals of pulmonary rehabilitation are to reduce symptoms, improve quality of life, and increase physical and emotional participation in everyday activities. It addresses a range of non-pulmonary problems that may not be adequately addressed by medical therapy for COPD. Such problems, which especially affect patients in Stage II (Moderate COPD) to Stage IV (Very Severe COPD), include relative social isolation, altered mood states (especially depression), muscle wasting and weight loss. These problems have complex inter-relationships. Improvement in any one of these processes can interrupt the "vicious circle" in COPD so that positive gains occur in all aspects of the illness.

Figure 1: The Cycle of Physical, Social and Psychosocial Consequences of COPD

Pulmonary rehabilitation has been carefully evaluated in a large number of clinical trials. The various benefits are summarised in Table 3.

Data suggest that these benefits can be sustained even after a single pulmonary rehabilitation program.
Benefits do wane after the rehabilitation program ends, but if exercise-training is maintained at home, the patientÕs health status remains above pre-rehabilitation levels. The 2003 report recommends at least two months for rehabilitation programs.

Table 3:
Benefits of Pulmonary Rehabilitation in COPD

Improves exercise capacity

Reduces the perceived intensity of breathlessness

Reduces the number and duration of hospitalisations

Reduces anxiety and depression associated with COPD

Improves survival

Oxygen Therapy

Oxygen therapy, one of the principal non-pharmacological treatments for patients with Stage IV (Very Severe COPD), can be administered in three ways:

Long-term continuous therapy
During exercise
To relieve acute dyspnoea.

The primary goal of oxygen therapy is to increase the baseline PaO2 to at least 8.0 kPa (60 mm Hg) at sea level and rest, and/or produce an SaO2 of at least 90%, which will preserve vital organ function by ensuring adequate delivery of oxygen.

The long-term administration of oxygen (more than 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival. It can also have a beneficial impact on haemodynamics, haematological characteristics, exercise capacity, lung mechanics and mental state. Several controlled prospective studies show that the primary haemodynamic effect of oxygen therapy prevents the progression of pulmonary hypertension.

Exacerbation

COPD is often associated with exacerbations of symptoms. In patients with Stage I (Mild) and Stage II (Moderate) COPD, an exacerbation is associated with increased breathlessness, often accompanied by increased cough and sputum production, and may require medical attention outside the hospital. The need for medical intervention intensifies as the airflow limitation worsens. Exacerbations in Stage IV (Very Severe) COPD are associated with acute respiratory failure, representing a significant burden on the health care system. Hospital mortality of patients admitted for an exacerbation of COPD is approximately 10%, and the long-term outcome is poor. Mortality reaches 40% in one year, and is even higher (up to 59%) for patients older than 65 years. These figures vary from country to country depending on the health care system and the availability of intensive care unit (ICU) beds.

The most common causes of an exacerbation (Table 4) are infection of the tracheobronchial tree and air pollution. However, the cause of about one-third of severe exacerbations cannot be identified. The role of bacterial infections, once believed to be the main cause of COPD exacerbations, is controversial. Conditions that may mimic an exacerbation include pneumonia, congestive heart failure, pneumothorax, pleural effusion, pulmonary embolism and arrhythmia.

Home Management of Exacerbation

There is increasing interest in home care for end-stage COPD patients, although economic studies of home-care services have yielded mixed results. Four randomised clinical trials have shown that nurse-administered home care represents an effective and practical alternative to hospitalisation in selected patients with exacerbations of COPD without acidotic respiratory failure. The algorithm reported in Figure 2 may assist in the management of an exacerbation at home; a step-wise therapeutic approach is recommended.

Table 4:
Common Causes of COPD Exacerbation

Primary

Tracheobronchial infection

Air pollution

Secondary

Pneumonia

Pulmonary embolism

Pneumothorax

Rib fractures / Chest trauma

Inappropriate use of sedatives, narcotics, beta-blocking agents

Right and/or left heart failure or arrhythmias

Table 5:
Medical History and Signs of Severity

Medical History
Signs of Severity

Duration of worsening or new symptoms

Number of previous episodes (exacerbations/ hospitalisations)

Present treatment regimen

Use of accessory respiratory muscles

Paradoxical chest wall movements

Worsening or new onset central cyanosis

Development of peripheral oedema

Haemodynamic instability

Signs of right heart failure

Reduced alertness

Hospital Management

The risk of dying from an exacerbation of COPD is closely related to the:

1. Development of respiratory acidosis
2. Presence of significant comorbidities
3. Need for ventilatory support.

While the absence of these features dilutes the risk of dying, those with severe underlying COPD often require hospitalisation in any case.
Attempts at managing such patients within the community have met with limited success. However, returning them to their homes with increased social support and a supervised medical care package after initial emergency room assessment has been much more successful. Several randomised controlled trials have confirmed that this is a safe alternative to hospitalisation, although it probably only applies to about 25% of COPD admissions. Savings on inpatient expenditures offset the additional costs of maintaining a community-based COPD nursing team.

Table 6: Indications for Hospital Assessment or Admission in Exacerbations of COPD
Marked increase in intensity of symptoms, such as sudden development of resting dyspnoea Onset of new physical signs (e.g., cyanosis, peripheral oedema) Severe background COPD Exacerbation not responding to initial medical management Significant co-morbidities Newly occurring arrhythmias Diagnostic uncertainties Old age Insufficient home support

Table 7: Indications for ICU Admission of Patients in Exacerbations of COPD
Severe dyspnoea that responds inadequately to initial emergency therapy Confusion, lethargy, coma Persistent or worsening hypoxemia (PaO2 < 5.3 kPa, 40 mm Hg), and/or severe worsening hypercapnia (PaCO2 > 8.0 kPa, 60 mm Hg), and/or severe/worsening respiratory acidosis (pH < 7.25) despite supplemental oxygen and NIPPV

Table 8: Management of Severe but Not Life-Threatening Exacerbations of COPD in the Emergency Department of the Hospital
Assess severity of symptoms, blood gases, chest X-ray
Administer controlled oxygen therapy and repeat arterial blood gas measurement after 30 minutes
Bronchodilators Increase doses or frequency Combine b2 agonists and anticholinergics Use spacers or air-driven nebulizers Consider adding intravenous aminophylline, if needed
Add oral or intravenous glucocorticosteroids
Consider antibiotics (oral or occasionally intravenous) if there are signs of bacterial infection
Consider non-invasive mechanical ventilation
At all times Monitor fluid balance and nutrition Consider subcutaneous heparin Identify and treat associated conditions (e.g., heart failure, arrhythmias) Closely monitor condition of the patient

Hospital Discharge and Follow-Up

Insufficient clinical data exist to establish the optimal duration of hospitalisation in individual patients developing an exacerbation of COPD. Consensus and limited data support the discharge criteria listed in Table 9. Table 10 provides items to include in a follow-up assessment four to six weeks after discharge from the hospital. Thereafter, follow-up is the same as for stable COPD, including supervising smoking cessation, assessing the effectiveness of each drug treatment and monitoring changes in spirometric parameters.

Table 9. Discharge Criteria for Patients with Exacerbations of COPD

Inhaled b2-agonist therapy is required not more frequently than every four hours

Patient, if previously ambulatory, is able to walk across the room

Patient is able to eat and sleep without frequent awakening by dyspnoea

Patient has been clinically stable for 12 to 24 hours

Arterial blood gases have been stable for 12 to 24 hours

Patient (or home caregiver) fully understands correct use of medications

Follow-up and home care arrangements have been completed (e.g., visiting nurse, oxygen delivery, meal provisions)

Patient, family and physician are confident that patient can be managed successfully

Table 10. Follow-up Assessment 4 to 6 Weeks After Discharge from Hospital for exacerbatuons of COPD

Ability to cope in usual environment

Measurement of FEV1

Reassessment of inhaler technique

Understanding of recommended treatment regimen

Need for long-term oxygen therapy
and/or home nebulizer
(for patients with very severe COPD)

If hypoxemia develops during exacerbation, arterial blood gases should be rechecked at discharge and at the follow-up visit. If the patient remains hypoxemic, long-term oxygen therapy should be instituted.

For further information log on to
www.goldcopd.com

Abridged Prescribing Information

Composition: Each actuation delivers Tiotropium bromide monohydrate equivalent to Tiotropium ............ 9 mcg Appropriate overages added.

Description: Tiotropium bromide is a long-acting, specific, muscarinic receptor antagonist, in clinical medicine often called an anticholinergic. By binding to the muscarinic receptors in the bronchial smooth musculature, tiotropium bromide inhibits the cholinergic (bronchoconstrictive) effects of acetylcholine, released from parasympathetic nerve endings. The long duration is probably due to the very slow dissociation from the M3 receptor, exhibiting a significantly longer dissociation half-life than ipratropium.

Indications: Tiotropium bromide is indicated in the maintenance treatment of chronic obstructive pulmonary disease (COPD).

Dosage and administration: The recommended dosage of tiotropium bromide is the inhalation of 2 puffs once daily of Tiova Inhaler . It is recommended to use Tiova Inhaler with a Zerostat Spacer.

Contraindications: Tiotropium bromide inhalation is contraindicated in patients with hypersensitivity to tiotropium bromide, atropine or its derivatives, e.g. ipratropium or oxitropium.

Warnings and precautions: Tiotropium bromide, as a once-daily maintenance bronchodilator, should not be used for the initial treatment of acute episodes of bronchospasm, i.e. rescue therapy.

Immediate hypersensitivity reactions may occur after administration of tiotropium bromide inhalation.

As with other anticholinergic drugs, tiotropium bromide should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.Inhaled medicines may cause inhalation-induced bronchospasm.

As plasma concentration increases with decreased renal function in patients with moderate to severe renal impairment (creatinine clearance 50 ml/min) tiotropium bromide should be used only if the expected benefit outweighs the potential risk. There is no long-term experience in patients with severe renal impairment.

Patients should be cautioned to avoid getting the spray into their eyes. They should be advised that this may result in precipitation or worsening of narrow-angle glaucoma, eye pain or discomfort, temporary blurring of vision, visual halos or coloured images in association with red eyes from conjunctival and corneal congestion. Patients should stop using tiotropium bromide and consult a physician immediately when signs and symptoms of narrow-angle glaucoma appear.

Dry mouth, which has been observed with anticholinergic treatment, may in the long- term be associated with dental caries. Tiotropium bromide should not be used more frequently than once daily.

Drug interactions: Although no formal drug interaction studies have been performed, tiotropium bromide inhalation has been used concomitantly with other drugs without adverse drug reactions. These include sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids, commonly used in the treatment of COPD.

The co-administration of tiotropium bromide with other anticholinergic-containing drugs has not been studied and is therefore not recommended.

Pregnancy and lactation: Tiotropium bromide should not be used in pregnant or nursing women unless the expected benefit outweighs any possible risk to the unborn child or the infant.

Adverse events: Several organ systems and functions are under control of the parasympathetic nervous system and thus can be affected by anticholinergic agents. Possible adverse events attributable to systemic anticholinergic effects include dry mouth, dry throat, increased heart rate, blurred vision, glaucoma, urinary difficulty, urinary retention, and constipation. In addition, local upper airway irritant phenomena were observed in patients receiving tiotropium bromide. An increased incidence of dry mouth and constipation may occur with increasing age.

The most common anticholinergic adverse reaction reported by COPD patients was dry mouth, which was mild in the majority of cases. In general, dry mouth had an onset between three and five weeks, which resolved while patients continued to receive tiotropium bromide. Discontinuation rates due to dry mouth were 0.3% (3 of 906 patients) of the treated patients from the one-year studies.

Overdose: High doses of tiotropium bromide may lead to anticholinergic signs and symptoms (see adverse events). However, there were no systemic anticholinergic adverse effects following a single inhaled dose of up to 340 micrograms tiotropium bromide in healthy volunteers. Additionally, no relevant adverse effects, beyond dry mouth, were observed following seven-day dosing of up to 170 micrograms tiotropium bromide in healthy volunteers.

Presentation: Sales pack is available in a canister containing 120 metered dose.

For the use only of a Registered Medical Practitioner or a Hospital or a Laboratory