Oxygen Toxicity: Pulmonary Toxicity (The ‘Lorrain Smith Effect’)

Clinically obvious pulmonary oxygen toxicity does not manifest in short-duration oxygen diving. It assumes greater importance in saturation and long chamber dives and where a high PO2 is inspired, such as in therapeutic recompression. Prolonged exposures to PO2 as low as 0.55 ATA (e.g. in space flight) have been found to produce significant changes. A PIO2 of 0.75 ATA has produced toxicity in 24 hours.

In animals, pulmonary oxygen poisoning causes progressive respiratory distress, leading to respiratory failure and finally death. The wide variation of tolerance among different species invalidates direct extrapolation of animal studies to humans, but early signs in humans are similar to those in animals. In patients receiving high concentrations of oxygen therapeutically, it is sometimes difficult to distinguish between the conditions for which the oxygen is given and the effects of oxygen itself (e.g. shock lung, respiratory distress syndrome).

Clinical manifestations

As in neurological toxicity, the factors affecting the degree of toxicity are the PIO2, the duration of exposure and individual variation in susceptibility. Exposure to 2.0 ATA oxygen produces symptoms in some normal humans at 3 hours, but the occasional individual may remain symptom free for up to 8 hours.

The earliest symptom is usually a mild tracheal irritation similar to the tracheitis of an upper respiratory infection. This irritation is aggravated by deep inspiration, which may produce a cough. Smoking has a similar result. Chest tightness is often noted; then a substernal pain develops that is also aggravated by deep breathing and coughing. The cough becomes progressively worse until it is uncontrollable. Dyspnoea at rest develops and, if the exposure is prolonged, is rapidly progressive. The higher the inspired oxygen pressure, the more rapidly symptoms develop and the greater is the intensity.

Physical signs, such as rales, nasal mucous membrane hyperaemia and fever, have been produced only after prolonged exposure in normal subjects.

Pulmonary oxygen toxicity

  • Chest tightness or discomfort.
  • Cough.
  • Shortness of breath.
  • Chest pain.

The measurement of forced VC (FVC or VC) is one monitor of the onset and progression of toxicity, although it is less sensitive than the clinical symptoms. Reduction in VC is usually progressive throughout the oxygen exposure. The drop continues for several hours after cessation of exposure and many occasionally take several days to return to normal. Because measurement of VC requires the subject’s full cooperation, usefulness may be limited in the therapeutic situation. Conversely, it is a useful tool in monitoring repeated exposures in hyperbaric workers. It has been used to delineate pulmonary oxygen tolerance limits in normal subjects – this is shown in Figure 17.3, which relates PO2 to duration of exposure. The percentage fall in VC is plotted. The size of the fall in VC does not always indicate the degree of pulmonary toxicity as measured by other lung function tests, such as other lung volumes, static and dynamic compliance and diffusing capacity for carbon monoxide. Changes in diffusing capacity may be the most sensitive indicator.

Pulmonary oxygen tolerance curves in normal men(based on vital capacity changes in 50% of the subjects)
Figure 17.3 Relationship of partial pressure of oxygen breathed and duration of exposure with degree of pulmonary oxygen damage. ΔVC, vital capacity change.

Exposure at 3 ATA for 3.5 hours caused chest discomfort, cough and dyspnoea in most of 13 subjects. There was no significant change in post-exposure FVC. Maximum mid-expiratory flow rates were reduced, but airway resistance did not change.

Some studies in divers have indicated that the reduction in forced mid-expiratory flow rates may persist for at least 3 years after deep saturation dives and also after shallow saturation dives with the same hyperoxic exposure profile. Forced expiratory volume in 1 second (FEV1) and FVC were not significantly altered.

Some individuals, especially at higher PIO2 (2.5 ATA), demonstrate a rapid fall in VC. The recovery after exposure is also more rapid than that after an equal VC decrement produced at a lower PO2 for a longer time.

Although chest x-ray changes have been reported, there is no pathognomonic appearance of oxygen toxicity. Diffuse bilateral pulmonary densities have been reported. With continued exposure, irregularly shaped infiltrates extend and coalesce.


The pathological changes in the lung as a result of oxygen toxicity have been divided into two types; acute and chronic7, depending on the PIO2.

Pressures of oxygen greater than 0.8 ATA cause a relatively acute toxicity that has been subdivided into exudative and proliferative phases. The exudative phase consists of a perivascular and interstitial inflammatory response and alveolar oedema, haemorrhage, hyaline membranes, swelling and destruction of capillary endothelial cells and destruction of type I alveolar lining cells. (This phase was the type described by Lorrain Smith.) Progression of the disease leads to the proliferative phase, which, after resolution of the inflammatory exudate, is characterized by proliferation of fibroblasts and type II alveolar cells. There is an increase in the alveolar-capillary distance. Pulmonary capillaries are destroyed, and some arterioles become obstructed with thrombus.

A more chronic response usually follows PIO2 between 0.5 and 0.8 ATA for longer periods. It is characterized by hyperplasia of type II cells, replacing type I cells and progressive pulmonary fibrosis, especially affecting alveolar ducts rather than alveolar septa. These features are also found in the adult respiratory distress syndrome (shock, drowning, trauma) for which high oxygen tensions are given. Whether oxygen actually causes the damage in these situations or exacerbates the condition by interacting with the initial pulmonary damage is not clear.

A consequence of these effects on pulmonary physiology is to increase ventilation-perfusion inequality. Obstruction of arterioles results in an increase in dead space.


No specific therapy is available that can be used clinically to delay or modify the pulmonary damage caused by hyperoxia. Intermittent exposure may delay the onset of toxicity. Delay of pulmonary toxicity has been demonstrated in humans. It has been suggested that the rate of recovery is greater than the rate of development of cellular changes leading to toxicity.

When toxicity is evident, the PO2 should be reduced. It is therefore important to be aware of the earliest signs of the syndrome.

Traditionally, the monitoring of VC has been employed as an indicator of toxicity. The maximum acceptable reduction in VC depends on the reasons for the exposure. Although a 20 per cent reduction may be acceptable in the treatment of severe DCS, a 10 per cent reduction would cause concern under operational diving conditions. One concept that has gained some popularity is that of the ‘UPTD’ or units of pulmonary toxic dose. UPTDs allow the expression of different exposures in time and PIO2 related to a ‘standard’ exposure at 1.0 ATA expressed in minutes. Expected UPTDs can be calculated for any planned exposure and that exposure can be modified to keep the decrement in VC within acceptable limits (see Clark and Thom7 for a fuller explanation).

The degree of oxygen toxicity equivalent to a 2 per cent decrease in VC (approximately the decrement predicted for a standard US Navy Treatment Table 6 treatment for DCS) is completely reversible, asymptomatic and very difficult to measure under ordinary circumstances. With the elevated pressures of oxygen used in the treatment of serious diseases, such as severe DCS or gas gangrene, it may be reasonable to accept a greater degree of pulmonary toxicity to treat the patient. The primary requirement of any therapy is that the treatment should not be worse than the disease.

Pulmonary toxicity that produces a 10 per cent decrease in VC is associated with moderate symptoms of coughing and pain in the chest on deep inspiration. This degree of impairment of lung function has been shown to be reversible within a few days. It is suggested that a 10 per cent decrement in VC be chosen as the limit for most hyperbaric oxygen therapy procedures.

VC is a relatively crude measure of toxicity. Forced mid-expiratory flow measurements or the less practical diffusing capacity for carbon monoxide may prove to be more sensitive indicators for repeated or long-term exposures.

Intermittent rather than continuous exposure to high oxygen pressure delays the onset of’ both neurological and pulmonary oxygen toxicity.

Adherence to proposed pressure-duration limits for pulmonary oxygen toxicity is difficult where extended durations and changing PO2 are involved.

Methods for calculating cumulative pulmonary toxicity have therefore been devised (e.g. the UPTD), and they may have a role in prolonged decompression and hyperbaric oxygen therapy.

As discussed in the previous section on prevention of neurological toxicity, many drugs have been shown to be effective in animal experiments. They may have a role in the future in the prevention of pulmonary and other oxygen toxicity, at least for hyperbaric therapy exposure.