Teaching Slide Set 2019: Global Initiative For Chronic Obstructive Lung Disease (Gold)
Teaching Slide Set 2019: Global Initiative For Chronic Obstructive Lung Disease (Gold)
Teaching Slide Set 2019: Global Initiative For Chronic Obstructive Lung Disease (Gold)
1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a
systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2095-128.
2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11): e442.
5. Management of Exacerbations
5. Management of Exacerbations
► European Union:
Direct costs of respiratory disease ~6% of the total
healthcare budget
COPD accounting for 56% (38.6 billion Euros) of the
cost of respiratory disease.
► USA:
Direct costs of COPD are $32 billion
Indirect costs $20.4 billion.
► Genetic factors
► Age and gender
► Lung growth and development
► Exposure to particles
► Socioeconomic status
► Asthma & airway hyper-reactivity
► Chronic bronchitis
► Infections
► Pathogenesis
Oxidative stress
Protease-antiprotease imbalance
Inflammatory cells
Inflammatory mediators
Peribronchiolar and interstitial fibrosis
► Pathophysiology
Airflow limitation and gas trapping
Gas exchange abnormalities
Mucus hypersecretion
Pulmonary hypertension
5. Management of Exacerbations
► Symptoms of COPD
► Classified as:
Mild (treated with SABDs only)
Moderate (treated with SABDs plus antibiotics and/or oral
corticosteroids) or
Severe (patient requires hospitalization or visits the emergency
room). Severe exacerbations may also be associated with acute
respiratory failure.
► Blood eosinophil count may also predict exacerbation rates (in
patients treated with LABA without ICS).
Example
AATD screening
5. Management of Exacerbations
5. Management of Exacerbations
► The main treatment goals are reduction of symptoms and future risk of
exacerbations.
Pharmacological treatment
► Pharmacological therapies can reduce symptoms, and the risk and severity of
exacerbations, as well as improve health status and exercise tolerance.
► Most of the drugs are inhaled so proper inhaler technique is of high relevance.
Pharmacological treatment
Pharmacological treatment
Pharmacological treatment
Definition of abbreviations: eos: blood eosinophil count in cells per microliter; mMRC: modified Medical Research
Council dyspnea questionnaire; CAT™: COPD Assessment Test™.
► In some patients, initial therapy with LABA/ICS may be the first choice.
► This treatment has the greatest likelihood of reducing exacerbations in
patients with blood eosinophil counts ≥ 300 cells/µL.
► LABA/ICS may also be first choice in COPD patients with a history of asthma.
► ICS may cause side effects such as pneumonia, so should be used as initial
therapy only after the possible clinical benefits versus risks have been
considered.
► Review
Review symptoms (dyspnea) and exacerbation risk.
► Assess
Assess inhaler technique and adherence, and the role of non-
pharmacological approaches (covered later in this chapter).
► Adjust
Adjust pharmacological treatment, including escalation or de-escalation.
Switching inhaler device or molecules within the same class (e.g., using a
different long acting bronchodilator) may be considered as appropriate.
Any change in treatment requires a subsequent review of the clinical
response, including side effects.
Dyspnea
► For patients with persistent breathlessness or exercise limitation on
long acting bronchodilator monotherapy, the use of two
bronchodilators is recommended.
If the addition of a second long acting bronchodilator does not
improve symptoms, we suggest the treatment could be stepped
down again to monotherapy. Switching inhaler device or molecules
can also be considered.
Dyspnea
► For patients with persistent breathlessness or exercise limitation on
LABA/ICS treatment, LAMA can be added to escalate to triple therapy.
Alternatively, switching from LABA/ICS to LABA/LAMA should be
considered if the original indication for ICS was inappropriate (e.g.,
an ICS was used to treat symptoms in the absence of a history of
exacerbations), or there has been a lack of response to ICS
treatment, or if ICS side effects warrant discontinuation.
► At all stages, dyspnea due to other causes (not COPD) should be
investigated and treated appropriately. Inhaler technique and
adherence should be considered as causes of inadequate treatment
response.
Exacerbations
► For patients with persistent exacerbations on long acting bronchodilator
monotherapy, escalation to either LABA/LAMA or LABA/ICS is recommended.
LABA/ICS may be preferred for patients with a history or findings suggestive of
asthma.
► Blood eosinophil counts may identify patients with a greater likelihood of a
beneficial response to ICS.
► For patients with one exacerbation per year, a peripheral blood level ≥ 300
eosinophils/µL identifies patients more likely to respond to LABA/ICS
treatment.13,14
► For patients with ≥ 2 moderate exacerbations per year or at least one severe
exacerbation requiring hospitalization in the prior year, LABA/ICS treatment can
be considered at blood eosinophil counts ≥ 100 cells/µL, as ICS effects are more
pronounced in patients with greater exacerbation frequency and/or severity.
Exacerbations
► In patients who develop further exacerbations on LABA/LAMA therapy
we suggest two alternative pathways. Blood eosinophil counts < 100
cells/µL can be used to predict a low likelihood of a beneficial ICS
response:
Escalation to LABA/LAMA/ICS. A beneficial response after the
addition of ICS may be observed at blood eosinophil counts ≥ 100
cells /µL, with a greater magnitude of response more likely with
higher eosinophil counts.
Add roflumilast or azithromycin if blood eosinophils < 100 cells/µL.
Exacerbations
► In patients who develop further exacerbations on LABA/ICS therapy, we
recommend escalation to triple therapy by adding a LAMA.
► Alternatively, treatment can be switched to LABA/LAMA if there has been
a lack of response to ICS treatment, or if ICS side effects warrant
discontinuation.
Exacerbations
► If patients treated with LABA/LAMA/ICS who still have exacerbations the
following options may be considered:
Add roflumilast. This may be considered in patients with an FEV1 < 50% predicted
and chronic bronchitis, particularly if they have experienced at least one
hospitalization for an exacerbation in the previous year.
Add a macrolide. The best available evidence exists for the use of azithromycin,
especially in those who are not current smokers. Consideration to the development
of resistant organisms should be factored into decision-making.
Stopping ICS. This can be considered if there are adverse effects (such as
pneumonia) or a reported lack of efficacy. However, a blood eosinophil count ≥ 300
cells /µL identifies patients with the greatest likelihood of experiencing more
exacerbations after ICS withdrawal and who subsequently should be followed
closely for relapse of exacerbations.
Physical activity
► Pulmonary rehabilitation, including community and home-based, is an
approach with clear evidence of benefits. However, the challenge is
promoting physical activity and maintaining it.
► There is evidence that physical activity is decreased in COPD patients. This
leads to a downward spiral of inactivity which predisposes patients to
reduced quality of life, increased rates of hospitalization and mortality.
► Behavior-targeted interventions with the aim of improving physical activity
should be encouraged.
► Most published studies to date provide little guidance for adaptation of
interventions for clinical care.
Pulmonary rehabilitation
► Patients with high symptom burden and risk of exacerbations (Groups B, C
and D), should be encouraged to take part in a formal rehabilitation
program that includes setting patient goals and is designed and delivered
in a structured manner, taking into account the individual’s COPD
characteristics and comorbidities.
► The components of pulmonary rehabilitation may vary but evidence-based
best practice for program delivery includes: structured and supervised
exercise training, smoking cessation, nutrition counseling, and self-
management education.
Exercise training
► A meta-analysis of RCTs found that exercise training alone, or with the
addition of activity counseling, significantly improved physical activity
levels in COPD patients.
► A combination of constant load or interval training with strength training
provides better outcomes than either method alone.
► Where possible, endurance exercise training to 60-80% of the symptom-
limited maximum work or heart rate is preferred, or to a Borg-rated
dyspnea or fatigue score of 4 to 6 (moderate to severe).
► Exercise training can be enhanced by optimizing bronchodilators, since
both LAMA and LABA have shown reduced resting and dynamic
hyperinflation.
Self-management education
► The basis of enabling patients to become active partners in their ongoing
care is to build knowledge and skills.
► Topics considered appropriate for an education program include:
Smoking cessation
Basic information about COPD
General approach to therapy and specific aspects of medical
treatment (respiratory medications and inhalation devices)
Strategies to help minimize dyspnea
Advice about when to seek help
Decision-making during exacerbations
Advance directives and end-of-life issues
Oxygen therapy
► Long-term oxygen therapy is indicated for stable patients who have:
PaO2 at or below 7.3 kPa (55 mmHg) or SaO2 at or below 88%, with or
without hypercapnia confirmed twice over a three-week period; or
PaO2 between 7.3 kPa (55 mmHg) and 8.0 kPa (60 mmHg), or SaO2 of
88%, if there is evidence of pulmonary hypertension, peripheral
edema suggesting congestive cardiac failure, or polycythemia
(hematocrit > 55%).
► Once placed on long-term oxygen therapy (LTOT) the patient should be re-
evaluated after 60 to 90 days with repeat arterial blood gas (ABG) or
oxygen saturation while inspiring the same level of oxygen or room air to
determine if oxygen is therapeutic and still indicated, respectively.
Oxygen therapy
► Long-term oxygen therapy is indicated for stable patients who have:
PaO2 at or below 7.3 kPa (55 mmHg) or SaO2 at or below 88%, with or
without hypercapnia confirmed twice over a three-week period; or
PaO2 between 7.3 kPa (55 mmHg) and 8.0 kPa (60 mmHg), or SaO2 of
88%, if there is evidence of pulmonary hypertension, peripheral
edema suggesting congestive cardiac failure, or polycythemia
(hematocrit > 55%).
► Once placed on long-term oxygen therapy (LTOT) the patient should be re-
evaluated after 60 to 90 days with repeat arterial blood gas (ABG) or
oxygen saturation while inspiring the same level of oxygen or room air to
determine if oxygen is therapeutic and still indicated, respectively.
5. Management of Exacerbations
► Antibiotics, when indicated, can shorten recovery time, reduce the risk of
early relapse, treatment failure, and hospitalization duration. Duration of
therapy should be 5-7 days.
No respiratory failure:
Respiratory rate: 20-30 breaths per minute; no use of accessory
respiratory muscles; no changes in mental status; hypoxemia
improved with supplemental oxygen given via Venturi mask 28-
35% inspired oxygen (FiO2); no increase in PaCO2.
Pharmacological treatment
The three classes of medications most commonly used for COPD exacerbations
are:
► Bronchodilators
Although there is no high-quality evidence from RCTs, it is recommended that
short-acting inhaled beta2-agonists, with or without short-acting
anticholinergics, are the initial bronchodilators for acute treatment of a COPD
exacerbation.
► Corticosteroids
Data from studies indicate that systemic glucocorticoids in COPD exacerbations
shorten recovery time and improve lung function (FEV1). They also improve
oxygenation, the risk of early relapse, treatment failure, and the length of
hospitalization.
► Antibiotics
5. Management of Exacerbations
► COPD often coexists with other diseases (comorbidities) that may have a
significant impact on disease course.
► Lung cancer is frequently seen in patients with COPD and is a main cause of
death.
► An increasing number of people in any aging population will suffer from multi-
morbidity, defined as the presence of two or more chronic conditions, and COPD is
present in the majority of multi-morbid patients.
► Multi-morbid patients have symptoms from multiple diseases and thus symptoms
and signs are complex and most often attributable to several causes in the chronic
state as well as during acute events.
► There is no evidence that COPD should be treated differently when part of multi-
morbidity; however, it should be kept in mind that most evidence comes from trials
in patients with COPD as the only significant disease.
► Treatments should be kept simple in the light of the unbearable polypharmacy that
these patients are often exposed to.