Is there airway obstruction when the FEV1 is normal?

I’ve been reviewing the literature on PFT interpretation lately and in doing so I ran across one of the issues that’s bothered me for a while. Specifically, my lab has been tasked with following the 2005 ATS/ERS guidelines for interpretation and using this algorithm these results:

Observed: %Predicted: LLN: Predicted:
FVC: 2.83 120% 1.76 2.36
FEV1: 1.77 100% 1.26 1.76
FEV1/FVC: 63 84% 65 75

would be read as mild airway obstruction.

Although it’s seems odd to have to call a normal FEV1 as obstruction I’ve been mostly okay with this since my lab has a number of patients with asthma whose best FVC and FEV1 obtained at some point in the past were 120% of predicted or greater but whose FEV1 frequently declines to 90% or 100% of predicted. In these cases since prior studies showed a normal FEV1/FVC ratio then an interpretation of a mild OVD is probably correct even though the FEV1 itself is well above the LLN, and this is actually the situation for this example.

In other cases, however this is a lot less clear. For example:

Observed: %Predicted: LLN: Predicted:
FVC: 3.83 127% 2.35 3.01
FEV1: 2.53 110% 1.75 2.30
FEV1/FVC: 66 86% 67 77

In this case, the FEV1 is much further above the LLN, the flow-volume loop is fairly normal and there are no prior spirometry results.

Anyway, while doing a Google Scholar search I found a letter to the editor that Dr. Paul Enright had written shortly after the ATS/ERS interpretation guidelines had been published. In this letter he criticized the guidelines over several issues but in particular for the decision to change how a reduced FEV1/FVC ratio with a normal FEV1 was interpreted.

In the 1991 ATS guidelines on interpretation the recommendation was to interpret a reduced FEV1/FVC ratio and a normal FEV1 (or at least one that was ≧100% of predicted) as “May be a physiological variant” and this was dropped from the 2005 guidelines. What this phrase referred to was the concept of dysanaptic lung growth that had been first proposed by Jere Mead around 1980 and is thought to occur when the alveolar tissue growth in an individual’s lungs outpaced the growth of their airways. His thought was that this developmental pattern would lead to an elevated FVC but a normal-ish FEV1. Mead based his conclusions on the results of physiological testing but animal studies since that time have shown that dysanaptic lung growth can occur following exposure to such things as nicotine during gestation, post-pneumonectomy and exposure to hypoxia during the period of developmental growth following birth.

The condition of an elevated FVC and reduced FEV1/FVC ratio appears to have been only rarely studied, however. The single study I’ve been able to find was performed relatively recent and was limited to 40 individuals. It’s conclusions could be read as supporting the 2005 ATS/ERS guidelines, although it was published several years after them. Using questionnaires most of the individuals were assigned to asthma, rhinitis or COPD groups with only a small minority designated as asymptomatic. Each subject performed plethysmographic lung volumes, DLCO, methacholine challenge, single-breath N2 washout as well as pre- and post-BD spirometry. As part of the findings the asthma and COPD groups showed signs of gas trapping and early airway closure, and a small minority from all groups showed signs of airway hyperresponsiveness (a significant response to methacholine or bronchodilator).

Realistically however, although the study showed differences in RV/TLC ratio, DLCO and closing volume that were statistically significant between some of these groups, the differences were subtle and unlikely to be evident in routine PFT testing. As importantly, there was no longitudinal PFT data so it isn’t possible to say whether the reduced FEV1/FVC ratio was due to the progression of an underlying lung disorder or whether it had always been present.

I think that Dr. Enright’s criticism has a lot of validity. Whether or not an individual with a reduced FEV1/FVC ratio and elevated FVC is due to dysanaptic lung growth or instead due to an obstructive lung disorder can only be conjecture (particularly if they are otherwise asymptomatic) unless there is clear evidence that the FEV1/FVC ratio had been normal at some time. I would note that at my lab a number of these individuals are sent for pulmonary function testing not because of any symptoms but instead because their chest x-ray is “abnormal”. In a couple of instances I can say it was specifically because their lung was abnormally long with a flat diaphragm which was interpreted by the radiologist as a sign of COPD but in retrospect may instead be due to an above-normal FVC.

We mostly take it for granted that the development of alveolar tissue and the airways are always proportional, and that both of these are proportional to height (well, along with age, gender and ethnicity). To a reasonable approximation this is true, but having said that there are always outliers and Mead’s observation provides an explanation for one group of these.

One of the long-standing problems in interpreting pulmonary function tests is that there is a certain amount of overlap between normal and abnormal lung function. Although there is still some disagreement about the actual threshold, a reduced FEV1/FVC ratio has long been considered to be a particularly reliable signal for the presence of airway obstruction. In this instance however, when the FVC is elevated a reduced FEV1/FVC ratio could likely be, as stated in the 1991 ATS guidelines, “a physiological variant” instead of being due to airway obstruction.

One final thought is that I find it interesting that the concept of dysanaptic lung growth does not appear to have ever been applied to individuals with normal FVC’s and reduced FEV1’s. It’s not that I have any particular doubt that disproportionate lung growth can occur, but if it is present in individuals with elevated FVC’s why can’t it also be present in individuals with normal FVC’s? And how would we be able to know the difference?

References:

ATS. Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis 1991; 144: 1202-1218.

Barisione G, Crimi E, Bartolini S, Saporiti R, Copello F, Pellegrino R, Brusasco V. How to interpret reduced forced expiratory volume in 1 s (FEV1)/vital capacity ratio with normal FEV1. Eur Respir J 2009; 33(6): 1396-1402.

Brusasco V, Crapo R, Viegi G. ATS/ERS Task Force: Standardisation of lung function testing. Interpretative strategies for lung function tests. Eur Respir J 2005; 948-968.

Enright P. Flawed interpretative strategies for lung function tests harm patients. Eur Respir J 2006; 27(6): 1322-1323.

Mead J. Dysanapsis in normal lungs assessed by the relationship between maximal flow, static recoil, and vital capacity. Am Rev Respir Dis 1980; 121: 339-342.

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9 thoughts on “Is there airway obstruction when the FEV1 is normal?

  1. This is where the actual flow volume loop is so helpful to have. If the loop looks normal, I don’t see any reason to fret about the actual numbers. The GOLD guidelines no longer consider the spirometry numbers or ratios to be the “be-all-end-all” for defining COPD severity in fact functional scores are now just as important.

    (pulmonary-critical care fellow)

    • Mohammed –

      In general I agree, but what constitutes a “normal” flow-volume loop? That is undefined particularly since what’s a normal flow-volume loop at age 70 is not what’s normal at age 30.

      – Richard

  2. Thank you for bringing this subject up. It also points out the importance of using normal values that are valid for the individual, as that can push the FEV1 in or out of the normal range, and thereby the interpretation of the test. I agree that the shape of the curve can be complicated with very young or old subjects. What is most important for the physiology, having a large enough FEV1, or matching your FEV1 and FVC?

    • Jenny –

      The bottom line is that the lung is the gas exchange organ of the body and its effectiveness depends on both ventilation and perfusion. The limiting factor for exercise is usually perfusion however, not ventilation. In this sense as long as ventilation is not unduly limited a reduced FEV1/FVC ratio with a normal FEV1 doesn’t really matter. The issue is that we expect the relationship between FEV1 and FVC to be stable across a wide range of lung volumes and there may be developmental reasons why this doesn’t always occur. It’s not necessarily pathological (or even abnormal) but it places limitations on what we can predict of lung function based on height (and age, gender and ethnicity) alone.

      Regards, Richard

  3. Interesting scenario, which we can also see in Cannabis smokers. Disproportionate increase in FVC secondary to Cannabis has been never explained well. Deep inspiratory training and THC related bronchodilatation have been proposed as caisuative factors. Studies also mentioned vital capacity reduction in heavy cannabis smokers (>20 joint years).

      • Richard,

        Please review the following studies.

        – Hancox RJ, Poulton R, Ely M. Welch D, Taylor DR, McLachlan CR et al. Effects of cannabis on lung function: a population-based cohort study. Eur Respir J.2010; 35:42-47.
        – Kempker, JA, Honig EG, Martin GS. The effects of marijuana exposure on respiratory health in U.S. Adults. Ann Am Thorac Soc 2015; 12(1):135-41.

      • Another important citation to review

        – Pletcher MJ, Vittinghoff E, Kalhan R, et al. Association Between Marijuana Exposure and Pulmonary Function Over 20 Years. JAMA. 2012 Jan 11;307(2):173–81.

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