Ventilatory response to hypoxia and hyperoxia

While reading a recently published article I found they had performed response to hypoxia and hyperoxia testing as part of the study. At one time or another in the past I’ve read about response to hypoxia testing but I’d never heard about hyperoxia testing before. I had some difficulty understanding their interpretation of the study’s results and for this reason I’ve spent some time reading up on the subject. I’m not sure this helped because there appears to be a lack of consensus not in only how to perform these tests but also in how they are interpreted, except perhaps in the most simplistic sense. Hypoxia and hyperoxia testing has been performed primarily to gain a deeper understanding of the way in which the peripheral (carotid) and central chemoreceptors function. There are a variety of sensor-feedback network models and results are often presented in terms of one model or another and this makes comparing results from different studies difficult. Interpretation and comparison is further complicated by the fact that results depend not only on the length of time that hypoxia or hyperoxia is maintained but whether the subject was exposed to hypoxia, hyperoxia or hypercapnia previously.

The ventilatory response to hypoxia tends to have three phases. First, once a subject begins breathing a hypoxic gas mixture within several seconds there is a rapid increase in minute ventilation known as the Acute Hypoxic Ventilatory Response (AHVR). Second, after several minutes there is a decrease in ventilation and this is usually called the Hypoxic Ventilatory Depression (HVD). Third, there is a progressive rise in ventilation after several hours which is related to acclimatization to altitude. It is the first phase, AHVR, that is most commonly measured during a hypoxic ventilatory response test. The actual length of time that is spent in any of these phases is widely variable between individuals and there is also a relatively large day-to-day variability within the same individual.
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When hypoventilation is the primary CPET limitation

Hypoventilation is defined as ventilation below that which is needed to maintain adequate gas exchange. It can be a feature in lung diseases as diverse as chronic bronchitis and pulmonary fibrosis but determining whether it is present of not is often complicated by defects in gas exchange. When desaturation occurs during a CPET (i.e. a significant decrease in SaO2 below 95%) this is a strong indication that the primary exercise limitation is pulmonary in nature and from that point the maximum minute ventilation and the Ve-VCO2 slope can show whether the limitation is ventilatory or instead due to a gas exchange defect. But in this circumstance what what does it mean when both the maximum minute ventilation and Ve-VCO2 slope are normal?

Recently a CPET came across my desk for an individual with chronic SOB. The individual recently had a full panel of pulmonary function tests:

Observed: %Predicted:
FVC (L): 1.73 62%
FEV1 (L): 1.39 66%
FEV1/FVC: 80 106%
TLC (L): 2.99 62%
DLCO (ml/min/mmHg): 14.66 84%
DL/VA: 5.45 124%
MIP (cm H2O): 11.5 18%
MEP(cm H2O): 21.3 24%

The reduced TLC showed a mild restrictive defect. At the same time the relatively normal DLCO indicates that the restriction is probably not due to interstitial lung disease and more likely either a chest wall or a neuromuscular disorder, both of which can prevent the thorax from expanding completely but where the lung tissue remains normal. The reduced MIP and MEP tends to suggest that a neuromuscular disorder is the more likely of the two.

I take this with a grain of salt however, and that is because this individual never had pulmonary function tests before and for this reason there is no way to know what their baseline DLCO was prior to the restriction. At the same time far too many individuals perform the MIP/MEP test poorly and low results are not definitive, and in this case in particular the results are so low the individual should have been in the ER, not the PFT Lab.

The CPET results were somewhat complicated, in that a close inspection showed both pulmonary and cardiovascular limitations.
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Asleep at the wheel

During this last week I was contacted by two different individuals who were asking for help in understanding their PFT results. In both cases they had a markedly elevated TLC and the interpretation included the notation that they had gas trapping and hyperinflation. Even though the amount of information they provided was minimal I am extremely skeptical that the TLC measurements were correct.

Gas trapping usually only occurs with severe airway obstruction. Hyperinflation, which at minimum consists of a chronically elevated FRC and RV, usually only occurs after prolonged gas trapping. An elevated TLC usually occurs only with prolonged hyperinflation and given the improvements in the care and treatment of COPD I’ve seen over the last several decades, has become relatively uncommon.

But one individual had perfectly normal spirometry:

%Pred:
FVC: 107%
FEV1: 112%
FEV1/FVC: 105%
TLC: 143%

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