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MMEF, FEF25-75%

Computation of MMEF (FEF25-75%)The MMEF (maximum midexpiratory flow) is the average expiratory flow over the middle half of the FVC. It should be taken from the blow with the largest sum of FEV1 and FVC (procedures, ref. 2). This index is very highly correlated with FEF50%FVC, so that one index offers no advantage over the other. The MMEF is in use as an index of airway obstruction, but this is fraught with hidden dangers:

  1. As MMEF = ½FVC/Δt (where Δt = time required to expire the middle half of the FVC), every disorder that affects the FVC will also influence the MMEF, just as in the case of MEFx%. During a forced expiration exhaled volume does not increase linearly with time; in the case of airway obstruction and reduced FVC the change in Δt, and therefore the severity of airway obstruction, is underestimated. It follows that the index is highly dependent on the validity of the FVC measurement and the level of expiratory effort.
  2. The reverse situation arises after bronchodilatation: the improvement in airway patency is underestimated by an increase in the FVC. It is even possible that the MMEF remains the same or even decreases when the FVC and the FEV1 increase appreciably after a bronchodilator drug. Assessing the MMEF isovolumetrically (at the same lung volume), i.e. by timing the interval taken to exhale the middle half of the largest FVC recorded before and after the intervention can circumvent this problem. Commonly available instruments do not provide facilities to this end.

These pitfalls also apply to longitudinal observations, unless the FVC would remain the same. An improvement in MMEF after administration of a bronchodilator, if not accompanied by an improvement in FEV1 and/or VC, should be disregarded (ref. 1). If MMEF is measured serially this should be done isovolumetrically (ref. 2), otherwise e.g. an improvement in FEV1 can be associated with paradoxical falls in MMEF. Another problem is that, depending on age, sex and ethnic group, the between subject coefficient of variation varies between 20-62% for FEF25-75% (ref.3), severely limiting its usefulness for clinical purposes.

Measurements of these flows are not clinically useful
Many people hold the view that FEF25-75% and FEF75% are more sensitive to airflow limitation than FEV1 or FEV1/FVC, because unlike these flows the latter indices are not sufficiently sensitive to "small airways disease". This idea arose because McFadden and Linden, who first launched this idea, based their conclusions on the erroneous, yet still popular assumption, that 80% of predicted defines the lower limit of normal (LLN). Yet, in childhood the LLN is at 65% predicted and in those >80 years at 37%.
Consider the following. Both FEV1 and FEF25-75% are average flows over the first 1 second and the middle half of the FVC, respectively. For practical purposes they virtually share the same expiratory flows in healthy people and subjects with airways obstruction. It is difficult to conceive how this would affect the FEF25-75% and not the FEV1. One might argue that as the FEV1/FVC ratio falls progressively below 0.75 so that flows are shared over a smaller portion of the FVC manoeuvre, FEF25-75% might be more affected. However, FEV1/FVC and FEF25-75% are very highly correlated (ref. 4). Not surprisingly, a large study showed that neither FEF25-75% nor FEF75% added information that could not be derived from FEV1, FVC and FEV1/FVC. These findings were subsequently corroborated in additonal studies (ref. 4).

Ref. 1 - Isolated improvement in FEF25-75%
  Berger R, Smith D. Acute postbronchodilator changes in pulmonary function parameters in patients with chronic airways obstruction. Chest 1988; 93: 541-546.
Ref. 2 - Assess serial measurements of FEF25-75% isovolumetrically
1 Olsen CR, Hale FC. A method for interpreting acute response to bronchodilators from the spirogram. Am Rev Respir Dis 1968; 98: 301-302.
2 Newball HH. The unreliability of the maximal midexpiratory flow as an index of acute airway changes. Chest 1975; 67: 311-314.
3 Sherter CB, Connolly JJ, Schilder DP. The significance of volume-adjusting the maximal midexpiratory flow in assessing the response to a bronchodilator drug. Chest 1978; 73: 568-571.
4 Stinson JM, McPherson GL, Darveaux R. Use of the isovolume FEF25-75% to assess small airway obstruction. Respir Care 1980; 25: 59-62.
5 Cockcroft DW, Berscheid BA. Volume adjustment of maximal midexpiratory flow: importance of changes in total lung capacity. Chest 1980; 78: 595-600.
6 Berger R, Smith D. Acute postbronchodilator changes in pulmonary function parameters in patients with chronic airways obstruction. Chest 1988; 93: 541-546.
Ref. 3 - Large coefficient of variation
  Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver B, Enright PL, Hankinson JL, Ip MSM, Zheng JP, Stocks J and the ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95 year age range: the Global Lung Function 2012 Equations. Eur Respir J 2012; 40: 1324–1343.
Ref. 4 - Measurements of these flows are not clinically useful
1 Quanjer PH, Weiner DJ, Pretto JJ, Brazzale DJ, Boros PW. Measurement of FEF25-75% and FEF75% does not contribute to clinical decision making. Eur Respir J 2014; 43: 1051-1058.
2 Pellegrino R, Brusasco V, Miller MR. Question everything. Eur Respir J 2014; 43: 947-948.
3 Boutin B, Koskas M. Guillo H, et al. Forced expiratory flows' contribution to lung function interpretation in schoolchildren. Eur Respir J 2015; 45: 107-115.
4 Lukiz KZ, Coates AL. Does the FEF25-75 or the FEF75 have any value in assessing lung disease in children with cystic fibrosis or asthma? Pediatr Pulmonol 2015; 50: 863-868.
Recommended procedures
Quanjer PhH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin R, Yernault JC. Lung volumes and forced ventilatory flows. Official Statement of the European Respiratory Society. Eur Respir J 1993; 6 suppl. 16: 5-40. Erratum Eur Respir J 1995; 8: 1629.
Miller MR et al. Standardisation of spirometry. ATS/ERS task force: standardisation of lung function testing. Eur Respir J 2005; 26: 319-338.
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