Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung. It is very prevalent (around 7% of the population) and a common cause of morbidity and mortality.

The disease may present as chronic bronchitis, emphysema, asthma in which the obstruction is not completely reversible, or a mixture of them.


  • Smoking
  • Indoor air pollution
  • Exposure to environmental substances: Particulate, gases, fumes, chemicals, dust.
  • Age and Sex: More common in women.
  • Airway responsiveness and Atopy
  • Bronchopulmonary dysplasia
  • Tuberculosis
  • Genetic and Molecular factors: Gene polymorphisms, metalloproteinase dysregulation, elastase excess.


Most common symptoms include shortness of breath (rest or exercise) and chronic cough with sputum production. They may occur together or independently in any order. Other symptoms such as fatigue, chest tightness and fever may be referred.

Physical examination may show cyanosis, increase in the anteroposterior thoracic diameter (barrel chest), decreased breath sounds, wheezing, crackles and increased resonance to percussion. Other findings may include use of accessory respiratory muscles and jugular venous distention during expiration.

During an exacerbation patients may have diffuse wheezing, crackles, tachycardia, tachypnea, and respiratory distress.


Every patient with a history suggestive of COPD should be evaluated with pulmonary function test (PFT) or spirometry. The exam should be performed before and after the administration of a bronchodilator, such as albuterol 400mcg (inhalation).

In PFTs, patients may have reduction of the FEV1/FVC and FEV1, indicative of obstruction. They also may have decreased inspiratory capacity (IC) and vital capacity, with increased total lung capacity. Diffusing capacity for carbon monoxide (DLCO), when performed, may be reduced.

Diagnosis is confirmed when FEV1/FVC ratio is less than 0.7 or less than the lower limit PLUS an FEV1 <80% of predicted that is not completely reversible by bronchodilator.

Chest radiography is useful and may help on the exclusion of other diagnosis. It may show hyperinflation, bullae, infiltrates and signs of pulmonary hypertension in late stages.

Chest CT scan is useful in patients with changes in the chest radiography on in those which different diagnosis such as pulmonary embolism is suspected.

Arterial blood gas is useful in patients with low FEV1 (<50 percent predicted), low oxygen saturation on pulse oximetry, acute exacerbation of COPD and altered mental status.

Alpha-1-antitrypsin deficiency should be ruled out in patients with COPD that are younger than 45 years.


Different staging systems were proposed for COPD.

The GOLD system is based on the FEV1, and it classifies the airflow obstruction in:

FEV1 > 80% predicted – Mild obstruction. (GOLD1)
FEV1 50-80% predicted – Moderate obstruction. (GOLD2)
FEV1 >30-<50% predicted – Severe obstruction. (GOLD3)
FEV1 <30% predicted – Very severe obstruction (GOLD4)

Since patients with COPD may have similar FEV1 but very different symptoms and morbidity, it is also important to assess symptoms when staging. To assess symptoms, tools such as mMRC questionnaire (see at the end) or COPD assessment test (CAT, see at the end) may be used. The new GOLD system took that into consideration. The new gold system classifies the patients in groups:

  • Group A: Low risk, less symptoms: Typically GOLD 1 or GOLD 2 (mild or moderate airflow limitation) and 0 to 1 exacerbation per year and no hospitalization for exacerbation; and CAT score <10 or mMRC grade 0 to 1.
  • Group B: Low risk, more symptoms: Typically GOLD 1 or GOLD 2 (mild or moderate airflow limitation) and 0 to 1 exacerbation per year and no hospitalization for exacerbation; and CAT score ≥10 or mMRC grade ≥2
  • Group C: High risk, less symptoms: Typically GOLD 3 or GOLD 4 (severe or very severe airflow limitation) and/or ≥2 exacerbations per year or ≥1 hospitalization for exacerbation; and CAT score <10 or mMRC grade 0 to 1.
  • Group D: High risk, more symptoms: Typically GOLD 3 or GOLD 4 (severe or very severe airflow limitation) and/or ≥2 exacerbations per year or ≥1 hospitalization for exacerbation; and CAT score ≥10 or mMRC grade ≥2.

Another staging system is the COPD Foundation system:

SG 0: Normal spirometry
SG 1 Mild: Post bronchodilator FEV1/forced vital capacity (FVC) ratio <0.7, FEV1 ≥60% predicted
SG 2 Moderate: Post bronchodilator FEV1/FVC ratio <0.7, 30% ≤FEV1 <60% predicted
SG 3 Severe: Post bronchodilator FEV1/FVC ratio <0.7, FEV1 <30% predicted
SG U Undefined: Post bronchodilator FEV1/FVC ratio >0.7, FEV1 <80% predicted

The BODE index (see at the end) may be used to estimate the 4 year survival of the patient.



Should be aimed at reducing symptoms, decreasing exacerbations and improving quality of life.

Smoking cessation is vital since it can reduce disease progression and improve symptoms.

In general, pharmacological therapy may include:

Short acting beta agonists: Short acting beta agonists (such as albuterol) can be prescribed as needed and are effective relieving symptoms and improving lung function. They can be used in association with short-acting anticholinergics (such as ipratropium).

Short acting anticholinergics: Can be used alone or, as mentioned, may be used in combination with a short-acting beta agonist.

Long-acting beta agonists (LABA): Long-acting bronchodilators (such as salmeterol, formoterol, indacaterol and others) may be used alone or in combination with inhaled steroids or LAMAs.

Long-acting muscarinic antagonist (LAMA): Long-acting anticholinergics (such as tiotropium, umeclidinium and others) have been used for a long time and are effective. They may be used alone or in combination. Example: SPIRIVA RESPIMAT (Tiotropium) two inhalations (5mcg) once a day.

Inhaled corticosteroids (ICS): ICSs (such as fluticasone) reduce inflammation, decreasing exacerbations and slowing symptom progression. They should ALWAYS be used in combination with long acting bronchodilators, never alone. Example: Fluticasone 500mcg/day (combine with LABA)

Theophylline: Oral theophylline may be tried in addition to the therapies mentioned before. Example: THEO ER (Theophylline sustained release) 400-600mg qDay.

PDE-4 inhibitors: Can be used in patients that have multiple exacerbations despite optimal treatment because they may reduce the number of exacerbations. An example is roflumilast (DALIRESP), 500mcg tablets once a day.

Mucolytics: Despite its common use in some countries, they are NOT routinely recommended. Example: N-acetyl cysteine, 600mg BID.

Chronic antibiotics: Usually NOT needed. Patients with recurrent exacerbations and bronchiectasis may benefit from prophylaxis with azithromycin 250mg three times per week.

Which medication to use and in which patient?

GOLD A patients should receive short-acting bronchodilators as needed as first line. Alternatively, patients could receive LAMA OR LABA or, as a last choice, theophylline.

GOLD B patients should receive short-acting bronchodilators as needed PLUS a long-acting bronchodilator. Alternatively, patient could receive LAMA + LABA. Theophylline can be added as third choice.

GOLD C patients should receive short-acting medications as needed PLUS LAMA or ICS + LABA. Alternatively, dual therapy with LABA + LAMA can be used. After that, PDE-4 inhibitor or theophylline are also alternatives.

GOLD D patients should receive short-acting medications as needed PLUS dual or triple therapy (ICS + LABA, LABA + LAMA or ICS + LABA + LAMA. Theophylline can be used if needed, as well as surgical treatments if indicated.

For patients that do not respond to a single long acting agent, a combination (ICS+LABA or LAMA+LABA) may produce better results. Even triple therapy (ICS+LABA+LAMA) may be considered.

ICS should be started for patients already with an optimized long-acting bronchodilation regimen but that still have symptoms and exacerbations or in patients with an asthma component.

Long term oxygen should be used when chronic hypoxemia is present. Chronic hypoxia is defined as a resting arterial oxygen tension (PaO2) ≤55 mmHg or SpO2 ≤88%. Another situations that may need oxygen include: PaO2 less than or equal to 59 mmHg, or an SpO2 less than or equal to 89%, if there is evidence of cor pulmonale, right heart failure, or erythrocytosis (hematocrit >55 percent) OR PaO2 of 59 mmHg or lower, or an SpO2 of 88%or lower, during exercise or sleep, in which case patients may benefit from supplemental oxygen during those times. The oxygen flow should aim to obtain a SpO2 of 90-92% (PaO2 60-65mmHg).

Pulmonary rehabilitation may benefit most of the patients, improving exercise capacity and quality of life.

Patients that do not respond to optimal therapy should have comorbid conditions ruled out, such as coronary artery disease, heart failure, pulmonary hypertension and pulmonary embolism.

Surgery (lung volume reduction or lung transplantation) may be indicated for a small number of patients. Patients may be put on the transplant list if they have at least one of the following: BODE index >= 7, FEV1 < 15-20% of predicted, three or more exacerbations in the previous year, one severe exacerbation with hypercapnic respiratory failure  or moderate to severe pulmonary hypertension.


Influenza vaccine annually

Pneumococcal vaccine PPSV23 once before 65 years, with a booster after 65 years and after that every 5 years.


An exacerbation is defined as an acute event with change in at least one of the cardinal symptoms:

  • Cough (increases in frequency and intensity)
  • Sputum productium (increases in volume or changes character)
  • Dyspnea increases/worsens

A “mild” exacerbation will have only one out of 3 symptoms. A “moderate or severe” will have at least 2 out of 3 symptoms.

Common triggers for exacerbation includes infection, viral or bacterial. Most common bacterias are Haemophilus, Moraxella, S. pneumoniae, Enterobacteriaceae and S. aureus. Most patients can be managed outpatient. However, a number of patients will require hospitalization. Patients with respiratory distress, acidosis, significant comorbidities, and response to previous treatment and inability to adherence are all reasonable indications for admission.

Before anything else, patients should have be evaluated regarding possible need of emergent intervention (airway, breathing and circulation).

Cardiac monitoring, pulse oximetry, BP monitoring and venous access should be obtained if needed. ABG should be collected and chest X-Ray obtained, as well as ECG, CBC, CMP, BNP, sputum tests and cultures if needed.

Supplemental oxygen should be provided, targeting a pulse oxygen saturation of 88 to 92% or PaO2 of 60 to 70 mmHg.

Short acting beta-adrenergic agonists (e.g. Albuterol 2.5mg diluted in 3 mL via nebulizer or 4-8 inhalations from MDI qHour) are used to produce bronchodilation and can be combined to short acting anticholinergic agents (e.g. Ipratropium 500 micrograms via nebulizer or 4-8 inhalations from MDI q4hours).

Systemic glucocorticoids therapy has a small but yet relevant benefit. Prednisone 40mg PO/day for 5 days may be used (or methylprednisolone 60-125mg IV q6-12hrs).

Antibiotics should be used only for moderate or severe cases (at least two of three cardinal symptoms). For these patients, a fluoroquinolone (Levofloxacin 750mg PO or IV daily) or a penicilim plus betalactamase inhibitor (Piperacilin-tazobactam 4.5g IV q6hrs) can be used if they have complicated COPD. If not, a macrolide, doxycycline or cephalosporin may be enough. Sputum cultures should be obtained. Failure to improve after 48-72 hours should prompt the medical team to consider different agents and maybe switch antibiotics.

Patients with suspected influenza should have oseltamivir 75mg PO q12hr (5 days) started.

Mechanical ventilation may be needed in patients with severe SOB and signs of respiratory muscle fatigue, worsening work of breathing and respiratory acidosis. Noninvasive mechanical ventilation may be tried first. If not tolerated, invasive ventilation should be started.


mMRC Dyspnea Scale

Grade 0                I only get breathless with strenuous exercise.
Grade 1                I get short of breath when hurrying on level ground or walking up a slight hill.
Grade 2                On level ground, I walk slower than people of the same age because of breathlessness or have to stop for breath when walking at my own pace.
Grade 3                I stop for breath after walking about 100 yards or after a few minutes on level ground.
Grade 4                I am too breathless to leave the house or I am breathless when dressing.

COPD Assessment Test (CAT)

Ask (or give patient a form) how te patient feels about his COPD in a scale between 0 (I am very happy) to 5 (I am very sad)

I never cough.
0 [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 [ ]
I cough all the time.

I have no mucus in my chest at all.
0 [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 [ ]
My chest is full of mucus.

My chest does not feel tight at all
0 [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 [ ]
My chest feels very tight.

When I walk up a hill or one flight of stairs I am not breathless.
0 [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 [ ]
When I walk up a hill or one flight of stairs I am very breathless.

I am not limited doing my activities at home.
0 [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 [ ]
I am very limited doing activities at home.

I am confident leaving my home despite my lung condition.
0 [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 [ ]
I am not at all confident leaving my house because of my long condition.

I sleep soundly.
0 [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 [ ]
I don`t sleep soundly because of my lung condition.

I have lots of energy.
0 [ ] 1 [ ] 2 [ ] 3 [ ] 4 [ ] 5 [ ]
I have no energy at all.

Add the points for the total score.

BODE Index for COPD survival prediction

FEV1 % Predicted After Bronchodialator

 >=65% (0 points)
50-64% (1 point)
36-49% (2 points)
<=35% (3 points)

6 Minute Walk Distance

>=350 Meters (0 points)
250-349 Meters (1 point)
150-249 Meters (2 points)
<=149 Meters (3 points)

MMRC Dyspnea Scale (4 is worst)

MMRC 0: Dyspneic on strenuous excercise (0 points)
MMRC 1: Dyspneic on walking a slight hill (0 points)
MMRC 2: Dyspneic on walking level ground; must stop occasionally due to breathlessness (1 point)
MMRC 3: Must stop for breathlessness after walking 100 yards or after a few minutes (2 points)
MMRC 4: Cannot leave house; breathless on dressing/undressing (3 points)

Body Mass Index

>21 (0 points)
<=21 (1 point)

Approximate 4 Year Survival Interpretation for BODE index.

0-2 Points:           80%

3-4 Points:           67%

5-6 Points:           57%

7-10 Points:        18%


  1. Global Initiative for Chronic Obstructive Lung Disease. 2017.
  2. Barreiro TJ, Perillo I. An Approach to Interpreting Spirometry. Am Fam Physician. 2004 Mar 1;69(5):1107-1115.
  3. Thomashow B, Crapo J, Yawn B, McIvor A, Cerreta S, Walsh J, Mannino D, Rennard S. The COPD Foundation Pocket Consultant Guide. J COPD F. 2014; 1(1): 83-87.
  4. Celli BR, Cote CG, Marin JM, et. al. The body-mass index, airflow obstruction, dyspnea and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004 Mar 4;350(10):1005-12.
  5. Weill D et al. A consensus document for the selection of lung transplant candidates: 2014–an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2015;34(1):1.
  6. Evensen AE. Management of COPD Exacerbations. Am Fam Physician. 2010 Mar 1;81(5):607-613.
  7. Garcia-Gutierrez S. Explicit criteria for hospital admission in exacerbations of chronic obstructive pulmonary disease. Int J Tuberc Lung Dis. 2011 May;15(5):680-6. doi: 10.5588/ijtld.10.0408.