Understanding COPD

21st January 2025

Chronic obstructive pulmonary disease (COPD) is literally a long-term (chronic) breathing disorder (disease) within the lungs (pulmonary) characterised by restricted airflow (obstructive).

COPD is characterised by poorly reversible airflow obstruction and an abnormal inflammatory response in the lungs (1, 2).  The latter represents the innate and adaptive immune responses to long-term exposure to noxious particles and gases, particularly cigarette smoke.  All cigarette smokers have some inflammation in their lungs, but those who develop COPD have an enhanced or abnormal response to inhaling toxic agents.

This amplified response may result in mucous hypersecretion (chronic bronchitis), tissue destruction (emphysema), and disruption of normal repair and defence mechanisms causing small airway inflammation and fibrosis (bronchiolitis).

Those with COPD often have exacerbations where there is a rapid and sustained worsening of symptoms beyond their usual day-to-day variation.

Pathophysiology

The syndrome of COPD is largely composed of

• Inflammation of the large and small airways combined with

• Destruction of the alveoli.

which is typically characterised by:

• Poorly reversible airflow obstruction and an abnormal inflammatory response in the lungs. 

• Protease and antiprotease imbalance.

• Oxidative stress.

Impaired airflow

An abnormal Inflammation response developed due to long-term exposure (e.g. cigarette smoke or workplace hazards. The significant number of inflammatory cells released, including neutrophils, macrophages, T Lymphocytes leads to a restriction of the large and small airways causing airflow obstruction.

These inflammatory cells also release inflammatory mediators – chemical signals – which cause an imbalance of protease and antiprotease.

Protease / Antiprotease Imbalance

Protease are enzymes which like to eat proteins - in the lungs this would be connective tissue. The destruction of cells does not sound like a great idea but is, in fact, essential; It is important in regulating some physiological and cellular processes including apoptosis, as well as preventing the accumulation of unwanted or misfolded proteins in cells. Consequently, abnormality in the regulation of proteolysis can cause disease.

Antiprotease is needed to regulate protease to prevent uncontrolled or unregulated damage.

Noxious stimuli trigger the release of more protease through inflammatory mediators whilst also inactivating antiprotease which leads to an imbalance allowing this dysregulated protease activity causing excessive cell destruction.

Oxidative Stress

Oxidants found in cigarette smoke and mediators released from inflammatory cells lead to more oxidants which:

• Further increases the inactivation of antiprotease, worsening the imbalance

• Further stimulation of mucous production

• Amplification of inflammatory processes

Consequence

1. Mucous hypersecretions and ciliary dysfunction produce a chronic productive cough, but difficult to clear because of the ciliary dysfunction.

2. Airflow obstructions – () Inhalation is an active process allowing airflow in but exhalation is passive and causes airways to collapse – trapping air - reducing inspiratory capacity and therefore functional residual capacity causing breathlessness and exercise intolerance. This presents as classic air trapping or hyperinflation where the casualty presents with difficulty exhaling rather than inhaling.

3. Gas exchange abnormality

   Airflow reaching alveoli (ventilation) is closely balanced to the amount of perfusion to allow optimum gaseous exchange “Ventilation:Perfusion (VQ) Ratio”

   In advanced stages of disease, this ratio can become disrupted due to alveoli damage and protease activity.

   VQ mismatch is where the degree of ventilation is not equal to the degree of perfusion:   At the extreme, there may be plenty of perfusion in a section of the lung but no ventilation due to collapsed alveoli and bronchioles – which is poor for gaseous exchange.  This is called “Shunt”.

   Elsewhere there may be poor perfusion due to vasoconstriction or arteriosclerosis - despite excellent ventilation – this is called “Dead Space” 

4. Pulmonary Hypotension – This develops late in COPD, at the time of severe gas exchange abnormalities.  Contributing factors include pulmonary arterial constriction (as a result of hypoxia), endothelial dysfunction, remodelling of the pulmonary arteries (smooth muscle hypertrophy and hyperplasia), and destruction of the pulmonary capillary bed.

   Structural changes in the pulmonary arterioles result in persistent pulmonary hypertension and right ventricular hypertrophy or enlargement and dysfunction.

Exacerbations (1, 2)

Exacerbation tends to be a worsening of the existing problems; worsening of airway inflammation, more mucous, further broncho-constriction leading to more ‘air trapping’ and occasional airway oedema.  This all results in reduced ventilation to the alveoli and hypoxic vasoconstriction of the pulmonary arterioles meaning less perfusion to the alveoli.  

This in, consequence, leads to worsening pulmonary gas exchange due to a deterioration in the already bad VQ ratio.

Furthermore; the prolonged increased respiratory effort causes respiratory muscle fatigue which, you guessed it, worsens alveoli ventilation.

The end result is hypoxia, hypercapnia respiratory acidosis and potentially death.

NICE define an exacerbation as ”a sustained worsening of the patients symptoms from their baseline which is acute (in a time period of less than 14 days) in onset.” (3)

Symptoms of Exacerbation include:

• Increased breathlessness

• Increased Cough

• Increased wheeze

• Increased inhaler use

• Tight chest

• Increased Sputum

• Change in sputum colour

• Fatigue

• Confusion
  

Assessment

Ask “How are things different to, say, two weeks ago?”   The person who best understands their condition is the casualty, this moment of impaired breathing could be perfectly normal to them.

Assessment of symptoms can be very subjective – comparison introduces a level of objectivity.  Ask “What is the furthest you have walked in the last 6 months without getting out of breath?” and  “How far have you been able to work today / since the exacerbation?”

The Medical Research Council Dyspnoea Scale can be used to trend casualties symptoms over a longer period of time, typically in a primary care setting but it could also be used to grade an Exacerbation.

Adapted from Fletcher CM, Elmes PC, Fairbairn MB et al. (1959) The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. British Medical Journal 2: 257–66.

Treatment

• Rest & reassure

• Encourage a comfortable position

• Access the casualty’s medication for them

• Consider supplemental oxygen to maintain a target of 885-92% SpO2

 Objectivity test before and after treatment:  How far can they count up from 1 in one breath?   Perform this before and after treatment.

What’s the deal with Supplemental Oxygen?

Oxygen administration in COPD is different from most casualties; historically it has been considered that excessive supplemental oxygen can remove the respiratory drive triggering acute hypercapnic respiratory failure.

A 2010 study (4)  identified a significant reduction in mortality (58%) when oxygen therapy is titrated versus high-flow (8-10 lpm via non-rebreather mask) oxygen therapy.

But why?

Previous Theory – Hypoxic drive

Historically this was believed to be due to Hypoxic drive; with normal lung function, stimulation to take another breath occurs when a patient has a slight rise in CO2; breathing is driven by a build-up of CO2 rather than a lack of 02.  The slight rise in CO2 stimulates the respiratory centre in the brain, creating the impulse to take another breath.  In some patients with a chronically high level of CO2, such as those with COPD, the stimulus and drive to breathe is caused by a decrease in O2.  This is called a hypoxic drive.  Thus, when oxygen is administered to patients with known CO2 retention, the provision of large amounts of O2 can actually cause their breathing to stop as there is no longer a desire to breath (5-7).

This is no longer considered to be a concern.

Current Theory:   VQ Mismatch & The Haldane Effect

Excessive supplemental oxygen can lead to hypercapnic respiratory failure and casualties with more severe hypoxia are at higher risk of developing CO2 retention.

One way supplemental oxygen can exacerbate symptoms is by affecting the body’s natural compensation mechanisms for VQ mismatch:

In chronic lung disease, where there are areas of poor ventilation in the lung, casualties compensate with vasoconstriction to reduce perfusion proportionate to the ventilation in the areas of hypoxia in the lungs to reduce shunt.

When excess oxygen is provided, blood flow shifts to poorly ventilated alveoli, increasing perfusion backup, increasing VQ mismatch, and shifting blood flow away from areas that were ventilating well, increasing physical dead space.

Another issue with excessive supplemental oxygen is the Haldane Effect.

Deoxygenated haemoglobin binds CO2 with a much stronger affinity than oxygenated haemoglobin.

Giving CPOD casualties supplemental O2 will convert their deoxyhaemoglobin to oxyhaemoglobin, binding oxygen and releasing CO2 into the blood at great levels.   Increased CO2 shifts the oxygen disassociation curve to the right, but due to their impaired breathing, they can’t increase minute ventilation to blow off the CO2 so CO2 levels rise (8).

 Further Reading - Supplemental Oxygen - Sometimes Less is More

Hospital or Home?

NICE Guidelines (3) Indicators for Treatment at Home versus Hospital (p45) provides some common-sense advice as to when a COPD casualty experiencing an exacerbation should be treated in hospital:

• Unable to cope at home

• Severe breathlessness

• Poor general condition

• Poor physical ability . confined to bed

• Cyanosis

• Worsening peripheral oedema

• Impaired level of consciousness

• Already receiving long-term oxygen therapy

• Living alone / not coping with independent living

• Acute confusion

• Rapid onset

• Significant comorbidity (particularly cardiac disease and insulin-dependent diabetes)

References

1. MacNee W.  (2006)  “Pathology, pathogenesis, and pathophysiology”. British Medical Journal.  20;332(7551):1202–4.

2. Lane ND, Brewin K, Hartley TM, Gray WK, Burgess M, Steer J, Bourke SC (2018)  “Specialist emergency care and COPD outcomes”.  BMJ Open Respiratory Research.  5:e000334.

3. NICE (2019) “Chronic obstructive pulmonary disease in over 16s: diagnosis and management“ https://www.nice.org.uk/guidance/ng115/resources/chronic-obstructive-pulmonary-disease-in-over-16s-diagnosis-and-management-pdf-66141600098245

4. Austin MA, Wills KE, Blizzard L, Walters EH, Wood-Baker R.  (2010)  “Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial.”  British Medical Journal.  Oct 18;341:c5462.

5. Kim, V; Benditt, JO; Wise, RA; Sharafkhaneh, A.  (2008). "Oxygen therapy in chronic obstructive pulmonary disease".  Proceedings of the American Thoracic Society. 5 (4): 513–8.

6. Patel, Dharmeshkumar N; Goel, Ashish; Agarwal, SB; Garg, Praveenkumar; Lakhani, Krishna K  (2003).  "Oxygen toxicity".  Journal, Indian Academy of Clinical Medicine. 4 (3): 234–7.

7. Doyle GR, McCutcheon JA. (2015).  "5.7 Cautions with Oxygen Therapy".  Clinical Procedures for Safer Patient Care.

8. Abdo WF, Heunks LM.  (2012)  “Oxygen-induced hypercapnia in COPD: myths and facts.”  Journal of Critical Care.  Oct 29;16(5):323.