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A58-year-old man with a history of hypertension and COPD presents to
the ED with complaints of increasing SOB, cough, sputum production, and
fever. He is treated with oxygen, bronchodilators, corticosteroids, and
empiric antibiotic therapy and then admitted to the hospital where
similar treatment is continued.
– Goal of therapy?
– Exacerbations of COPD, evidences?
– Optimal pharmacotherapeutic regimen?
– Non-pharmacologic Rx?
– Monitor & evaluate?
It is a common, preventable and treatable disease
– Characterized by persistent respiratory symptoms and airflow
– Airflow limitation is not fully reversible and is both chronic and
– Causes significant extra-pulmonary effects
– **that is due to airway and/or alveolar abnormalities usually
caused by significant exposure to noxious particles or gases.
Currently the 4th leading cause of death in the world1
Projected to be the 3rd leading cause of death by 20202
>3 million people died of COPD in 2012 accounting for 6% of all
~~24 million Americans
Globally, the its burden is projected to increase in coming decades
– Continued exposure to COPD risk factors and aging of the
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.
Prevalence of COPD
– Estimated 384 million COPD cases in 2010.
– Estimated global prevalence of 11.7% (95% CI 8.4%–15.0%).
– Three million deaths annually.
– With increasing prevalence of smoking in developing countries, and
aging populations in high-income countries
– By 2030 predicted 4.5 million COPD related deaths annually.
Prevalence of COPD...
– Systematic review and meta-analysis (Halbert et al, 2006)
– Included studies carried out in 28 countries between 1990 and 2004
– Prevalence of COPD was higher in smokers and ex-smokers
compared to non-smokers
– Higher ≥ 40 year group compared to those < 40
– Higher in men than women.
Economic burden of COPD
– Associated with significant economic burden.
– Exacerbations account for the greatest proportion of the total COPD
– European Union:
– Direct costs of respiratory disease ~6% of the total
– COPD accounting for 56% (38.6 billion Euros) of the cost of
– Direct costs of COPD are $32 billion
– Indirect costs $20.4 billion.
Global Burden of Disease (GBD) study
– High disability-Adjusted Life Year (DALY)
– It is an increasing contributor to disability & mortality
around the world.
– In 2013, COPD was 5th leading cause of DALYs lost.
– In the US, COPD is the 2nd leading cause of reduced DALYs,
trailing only ischemic heart disease
– *Cough on most days for at least 3 months of the year for at least 2
– *Associated with chronic or recurrent excessive mucus secretion into the
– **Abnormal permanent enlargement of the airspaces distal to the terminal
bronchioles accompanied by destruction of their walls
– Main risk factor: tobacco smoking
– (85% to 90% of cases)
– Only 15% to 20% of them
– 12X of non-smokers
– Other: environmental exposures such as
biomass fuel exposure and air pollution
– Host factors: genetic abnormalities,
abnormal lung dev’t & accelerated aging
The inflammation of COPD is often neutrophilic in nature.
– But, macrophages and CD8+ lymphocytes have major roles
– Others: TNF-α, IL-8, LT-B4
Stimulus for activation: exposure to noxious particles and gas
Others: oxidative stress, imbalance proteases and anti-proteases
S & Sxs: dyspnea, chronic cough or sputum production, and/or a hx
of exposure to risk factors.
Spirometry: post-bronchodilator FEV1/FVC < 0.70 confirms the
presence of persistent airflow limitation.
Concomitant chronic diseases
Clinical pictures, P/E, Necessary laboratory tests
Symptoms of COPD
– Chronic and progressive dyspnea
– Sputum production
– Wheezing and chest tightness
– Others – including fatigue, weight loss,
anorexia, syncope, rib fractures, ankle
swelling, depression, anxiety.
Key indicators for considering for diagnosis of COPD
Patient’s exposure to risk factors
Past medical history
Family Hx of COPD or other chronic respiratory disease.
Pattern of symptom development
Hx of exacerbations or previous hospitalizations for respiratory disorder
Presence of comorbidities
Impact of disease on patient’s life
Social and family support available to the patient.
Possibilities for reducing risk factors, especially smoking cessation.
A patient with advanced hypoxic COPD with central cyanosis. Pitting ankle oedema is a feature of cor pulmonale
Gross tar staining of the fingers due to chronic cigarette smoking. Tar staining and finger clubbing
Consider two patients:
– Both patients with FEV1 < 30% of predicted
– Both with CAT scores of 18
– But, one with 0 exacerbations in the past year and the other with 3
exacerbations in the past year.
Both would have been labelled GOLD D in the prior classification
With the new proposed scheme, the subject with 3 exacerbations in the
past year would be labelled GOLD grade 4, group D.
The other patient, who has had no exacerbations, would be classified as
GOLD grade 4, group B.
Smoking Cessation: greatest role
Vaccination (Pneumococcal & influenzae, others)… PCV13 & PPSV23
– Recommended for all patients ≥ 65 years of age
Long-term oxygen therapy
Long-term non-invasive ventilation...in severe chronic hypercapnia
Surgical or bronchoscopic interventional...Emphysema
Education and self-management
End of life and palliative care
Education and self-management
Healthcare professionals should be a major component of the “Chronic
Care Model” within the context of the healthcare delivery system.
Aim : motivate, engage and coach the patients to positively adapt their
health behavior(s) and develop skills to better manage their disease.
Long-term oxygen therapy is indicated for stable patients who have:
PaO2 ≤ 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 55 to 60 mmHg, or SaO2 of 88%, if there is evidence of
pulmonary hypertension, peripheral edema suggesting CHF or
polycythemia (hematocrit > 55%.
Prescription of supplemental oxygen to COPD patients
Interventional bronchoscopy and surgery
In emphysema and significant hyperinflation refractory to optimized
medical care...lung volume reduction
In selected patients with a large bulla, surgical bullectomy may be
In selected patients with very severe COPD and without relevant
contraindications, lung transplantation may be considered.
A proposed inititation, then subsequent escalation and/or de-escalation
– Only oxygen..!?
Relax bronchial smooth muscle,
Improve lung emptying,
Reduce thoracic hyperinflation at rest and during exercise,
Improve exercise tolerance
SABDs: relieve symptoms and increase exercise tolerance
LABDs: relieve symptoms, reduce exacerbation frequency, and improve
quality of life and health status
Example: LABAs by 23%
Tiotropium by 29%
ICs by 22%,
ICs + LABAs by 28%
β2-agonists, Anticholinergics, Methylxanthines
SABA + SAMA
– Tiotropium bromide
Includes: theophylline, aminophylline
Considered for patients who are intolerant or unable to use an inhaled
Have multiple mechanisms (bronchodilation and antiinflammatory)
Offer improvements in lung function, vital capacity, FEV1, and gas
Chronic systemic corticosteroid therapy should be avoided, if possible
– Reduction in capillary permeability to decrease mucus,
– Inhibition of release of proteolytic enzymes from leukocytes,
– Inhibition of prostaglandins.
Appropriate situations to consider
– Short-term systemic use for acute exacerbations
– Inhalation therapy for chronic stable COPD in selected patients.
Side effects from corticosteroids
– Muscular atrophy,
– thinning of the skin,
– Development of cataracts,
– Adrenal suppression and insufficiency
– Hoarseness, sore throat, oral candidiasis, and skin bruising
– Following the disappointing results of chronic ICS studies
progressive decline in lung function
– LABA + ICS: associated with greater improvements in clinical
outcomes [FEV1, health status, & frequency of exacerbations]
• Salmeterol + fluticasone
• Budesonide+ formoterol,
• Mometasone + formoterol
Phosphodiesterase 4 (PDE4)
– Responsible for degrading cAMP
– Production of TNF-α and IL-8.
– Example: roflumilast [500 mcg orally once a day]
– Recommended in severe or very severe COPD (Group C, D)
– Side effects: weight loss neuropsychiatric effects [ suicidal thoughts,
insomnia, anxiety, and new or worsened depression]
– Should be offered bronchodilator Rx
based on its effect on breathlessness.
– This can be either a short- or a long-
– This should be continued if symptomatic
benefit is documented.
– Initial therapy: long acting bronchodilator.
– LABD are superior to SABD taken as
needed, are therefore recommended.
– For patients with persistent breathlessness
on monotherapy the use of two
bronchodilators is recommended.
Group B (continued)
– For patients with severe breathlessness
initial therapy with two bronchodilators
may be considered.
– If the addition of a second
bronchodilator does not improve
symptoms, we suggest the treatment
could be stepped down again to a
– Group B patients are likely to have
comorbidities that may add to their
symptomatology and impact their
prognosis, and these possibilities should
– Initial therapy: a single long acting
– Patients with persistent exacerbations
LABA+ LAMA or LABA+ICS.
– As ICS increases the risk for developing
pneumonia in some patients, primary choice
– Recommendations tarting therapy with a
LABA/LAMA combination because:
– If a single bronchodilator is chosen as initial
treatment, a LAMA is preferred for
exacerbation prevention based on
comparison to LABAs
– A LABA + LAMA combination was superior
to a LABA + ICS combination in preventing
exacerbations and other patient reported
outcomes in Group D patients
– Group D patients are at higher risk of
developing pneumonia when receiving
treatment with ICS.
Group D (continued)
– In some patients initial therapy with LABA/ICS
e.g. asthma-COPD overlap.
– High blood eosinophil counts may be
considered as a parameter to support the use
– In patients who develop further
exacerbations on LABA/LAMA therapy ....two
– Escalation to LABA/LAMA/ICS.
– Switch to LABA/ICS. If LABA/ICS therapy
does not positively impact
exacerbations/symptoms, add LAMA.
Group D (continued)
– If patients treated with LABA/LAMA/ICS
still have exacerbations the following
options may be considered:
– Add roflumilast.
– Add a macrolide.
– Stopping ICS.
Monitoring disease progression and development of complications
Measurements. Decline in FEV1 can be tracked by spirometry performed
at least once a year.
Symptoms. At each visit, information on symptoms since the last visit
should be collected, including cough and sputum, breathlessness, fatigue,
activity limitation, and sleep disturbances.
Exacerbations. The frequency, severity, type and likely causes of all
exacerbations should be monitored.
Imaging. If there is a clear worsening of symptoms, imaging may be
Smoking status. At each visit, the current smoking status and smoke
exposure should be determined followed by appropriate action.
Pharmacotherapy and other medical treatment
Monitoring should focus on:
Dosages of prescribed medications.
Adherence to the regimen.
Effectiveness of the current regime.
Treatment modifications should be recommended.
Defn: an acute worsening of respiratory symptoms that result in
It is change in the patient’s baseline symptoms
– …..dyspnea, cough, or sputum production
– Sufficient to warrant a change in management
– Lung hyperinflation worsened worsening dyspnea &
poor gas exchange.
– Profound hypoxemia & hypercapnia respiratory acidosis
and respiratory failure.
• 1 cardinal sxs**
• Rx with SABDs only
Moderate/type 2Moderate/type 2
•2 cardinal sxs
•Rx with SABDs + abx and/or oral corticosteroids
• 3 cardinal sxs
• Require Hospitalization/ ER; risk of respiratory failure
**plus at least one of the following: URTI within 5 days, fever without other explanation, increased wheezing, increased
cough, increase in respiratory or heart rate >20% above baseline
– Prevention of hospitalization or reduction in hospital stay,
– Prevention of acute respiratory failure and death,
– Resolution of exacerbation sxs and a return to baseline clinical
status and quality of life.
– Intensification of bronchodilator therapy
– Short course of systemic corticosteroids.
– Antimicrobial: in the presence of selected symptoms
Controlled Oxygen Therapy: Titrate oxygen to desired oxygen
Noninvasive Mechanical Ventilation
Bronchodilators: Doses and frequency increased: SABDs preferred
Systemic corticosteroids: short course (7-14 days)
Antimicrobial Therapy: as Respiratory infections a cause for
– Most common cause: H.influenzae/para-influenzae, M.
catarrhalis, S.pneumoniae, including MDR pathogens, enteric
Maintenance therapy with long-acting bronchodilators should be initiated
as soon as possible before hospital discharge.
Systemic corticosteroids can improve lung function (FEV1), oxygenation and
shorten recovery time and hospitalization duration. Duration of therapy
should not be more than 5-7 days.
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 ~~ 10 days
Methylxanthines are not recommended due to increased side effect
COPD often coexists with other diseases (comorbidities) that may have a
significant impact on disease course.
In general, the presence of comorbidities should not alter COPD
treatment and comorbidities should be treated per usual standards
regardless of the presence of COPD.
Lung cancer is frequently seen in patients with COPD and is a main
cause of death.
Cardiovascular diseases are common and important comorbidities in
Osteoporosis and depression/anxiety are frequent, important
comorbidities in COPD, are often under-diagnosed, and are associated
with poor health status and prognosis.
Gastroesophageal reflux (GERD) is associated with an increased risk of
exacerbations and poorer health status.
When COPD is part of a multimorbidity care plan, attention should be
directed to ensure simplicity of treatment and to minimize
Some common comorbidities occurring in patients with COPD with
stable disease include:
– Heart failure, Ischemic heart disease (IHD)
– Arrhythmias, Peripheral vascular disease
– Anxiety and depression
– COPD and lung cancer
– Metabolic syndrome and diabetes
– Gastroesophageal reflux (GERD)
– Obstructive sleep apnea
Those with partially reversible airflow obstruction, an atopic symptoms,
and minimal smoking history