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Eur Respir J 2004; 24:890-891
Copyright ©ERS Journals Ltd 2004

End points for pulmonary arterial hypertension: a way backward

M. Sofia1, M. Maniscalco1, P. Carratù2 and O. Resta2

1 Dept of Respiratory Disease, University Federico II, Naples, and 2 Dept of Respiratory Disease, University of Bari, Bari, Italy.

To the Editors:

In the June 2004 issue of the European Respiratory Journal, Peacock et al. 1 recognised the need for end points, other than the assessment of functional capacity with the 6 min walking test, in pulmonary arterial hypertension (PAH) clinical trials. In their looking forward, the authors did not mention any role of the diffusing lung capacity for carbon monoxide (DL,CO) test, which was originally devised in 1909–1915 2. However, as recently reviewed 2, 3, the measurement of lung gas transfer for CO (TL,CO) holds some premise into the evaluation of patients with PAH. In daily clinical practice, TL,CO is derived from the product of constant rate of alveolar to blood CO uptake and the accessible alveolar volume, which is usually preserved in PAH; the examination of these two components allows exploration of the pathophysiological mechanism of TL,CO decrease at any time, due to pulmonary vascular abnormalities. Furthermore, the physiology of CO transfer is governed by the Roughton-Forster equation 4, partitioning the resistances to CO into membrane and red cell contributions, the latter accounting with appropriate calculations for 70–80% of total resistance 3. Moreover, the DL for CO or another suitable gas with greater haemoglobin affinity, such as nitric oxide, could be assessed at rest and during exercise, in combination with noninvasive measurement of cardiac output, providing sensitive indicators of the diffusive oxygen transport effectiveness, and structural alteration of the alveolar-capillary barrier 5, 6. Therefore, it seems logical to assume abnormalities in DL recruitment (or DL/cardiac output ratio) occurring in PAH before chronic cardiac consequences would be detected during echocardiography. Accordingly, DL,CO decrease at rest is present in 80% of PAH patients 7, and it is significantly related to the main cardiopulmonary exercise test parameters of aerobic function 8, which, in turn, are relevant to the prognosis of PAH 9.

In conclusion, following the authors' suggestions, we believe that diffusing lung capacity tests, combined in parallel with other markers, should receive consideration for as broader an application as possible for markers of pulmonary arterial hypertension. Hopefully, a view backward may widen the way forward.

References

  1. Peacock A, Naeije R, Galie N, Reeves JT. End points in pulmonary arterial hypertension: the way forward. Eur Respir J 2004;23:947–953.[Abstract/Free Full Text]
  2. Hughes JMB, Bates DV. Historical review: the carbon monoxide diffusing capacity (DL,CO) and its membrane (DM) and red cell (Theta-Vc) components. Respir Physiol Neurobiol 2003;138:115–142.
  3. Hughes JMB. The single breath transfer factor (TL,CO) and the transfer coefficient (KCO): a window onto the pulmonary microcirculation. Clin Physiol Funct Imaging 2003;23:63–71.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  4. Roughton FJW, Forster RE. Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lungs, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in lung capillaries. J Appl Physiol 1957;11:290–302.[Abstract/Free Full Text]
  5. Hsia CC. Coordinated adaptation of oxygen transport in cardiopulmonary disease. Circulation 2001;104:963–969.[Free Full Text]
  6. Hsia CC. Recruitment of lung diffusing capacity: update of concept and application. Chest 2002;122:1774–1783.[Abstract/Free Full Text]
  7. Steenhuis LH, Groen HJM, Koeter GH, van der Mark TW. Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension. Eur Respir J 2000;16:276–281.[Abstract]
  8. Sun XG, Hansen JE, Oudiz RJ, Wasserman K. Pulmonary function in primary pulmonary hypertension. J Am Coll Cardiol 2003;41:1028–1035.[Abstract/Free Full Text]
  9. Wenzel R, Opitz CF, Anker SD, et al. Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing. Circulation 2002;106:319–324.[Abstract/Free Full Text]




This Article
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