Late Lung Reactions

Late effects of the lung have been studied extensively in humans and animal models.

Arrangement of the Lung

The functional subunits of the lung are groups of alveoli serviced by a single respiratory bronchiole. There are, therefore, numerous FSUs within the lung tissue which explains its significant volume effect.

Endpoints for normal lung effects

There are two endpoints normally quoted for lung effects:

  • Radiation pneumonitis, a subacute effect
  • Lung fibrosis, a late effect

Radiation pneumonitis

Radiation pneumonitis is a potentially fatal condition caused by inflammation of lung in response to radiation.

Clinical symptoms

There are is a broad spectrum of severity and corresponding symptoms. Mild cases may be asymptomatic or have a dry cough. Moderate cases may complain of a productive cough (possibly with haemoptysis), fevers or mild breathlessness. Severe cases present with severe dyspnoea requiring admission for respiratory support.

Imaging features

Chest X-ray may show increased opacity in the radiation portal, although changes may involve other areas of the lung (see The Abscopal Effect). CT scans shows ground glass opacity in the affected area.

Pathological features

Microscopically, the alveoli are filled with an inflammatory infiltrate. Unlike other causes of pneumonitis, there is evidence of radiation effect, with bizarre type II pneumocytes and fibroblasts.

Clinical course

Most cases respond without treatment, and more severe cases will usually respond to corticosteriods. Symptoms do not generally last beyond 6 months. Occasionally, pneumonitis may be progressive and fatal. Patients will nearly always develop radiation fibrosis in the affected area.

Radiation fibrosis of the lung

Radiation fibrosis of the lung occurs months to years after radiation exposure, is a common sequelae of radiation pneumonitis but may occur without without it.

Clinical Features

The symptoms caused by fibrosis of the lung are related to the amount of lung involved. Small areas are asymptomatic, only seen on routine imaging. Larger areas may cause dyspnoea and a dry cough.

Imaging Features

On plain x-ray, the affected lung may appear normal or may show increased markings. Dense fibrosis and scarring may cause retraction of the lung and neighbouring organs. CT shows similar features.

Pathological Features

Histopathology shows obliteration of alveoli and replacement with fibrous tissue. The remaining vessels are abnormal with hyalinisation.

Clinical course

Fibrosis is usually permanent, but rarely involves the lung outside of the treatment area. The severity is highly dependent on the amount of lung involved.

Scoring systems


Grade 0 Grade 1 Grade 2 Grade 3 Grade 4 Grade 5
No effect Asymptomatic or mild symtpoms
Silent x-ray findings
Moderate symptomatic pneumonitis
fibrosis, low fever,
patchy consolidation
Severe symptoms;
Confluent x-ray findings
Severe insufficiency
Requiring O2
Assisted ventilation



Radiobiological Tolerance of Lung

Effect of Total Dose and Volume

The lung is a sensitive organ with a pronounced volume effect due to the parallel arrangement of its function subunits. The latest data on lung toxicity, released in the QUANTEC papers in 2010, has the following dose / response guidelines:

Dose to Lung
(Conventional Fractionation)
Risk of Symptomatic Pneumonitis
V20 < 30% < 20%
Mean 7 Gy < 5%
Mean 13 Gy 10%
Mean 20 Gy 20%
Mean 24 Gy 30%
Mean 27 Gy 40%

Effect of Fractionation

The lung has a low alpha/beta ratio, in the order of 3 Gy. This means that large fraction sizes are likely to cause significantly more damage; with a single dose of 10 Gy to both lungs the rate of pneumonitis approaches 50 - 60%.

Summary of Lung Tolerance

The lung responds to radiation in a subacute (radiation pneumonitis) and late fashion (radiation fibrosis). The lung is sensitive but small volumes can be treated to high dose with minimal risk of long term morbidity. Radiation pneumonitis is the dose limiting endpoint; lung fibrosis tends to occur in irradiated areas but varies considerably in severity (mostly dependent on the volume of lung irradiated).

Back to Late Effects in Normal Tissues