Pulmonary hypertension associated with idiopathic pulmonary fibrosis: morphofunctional characteristics of pulmonary artery branches and their relationship with functional cardiorespiratory status

The aim of the study was to investigate functional status of cardiorespiratory system and post-mortem morphometric characteristics of the heart and the lung arteries in secondary pulmonary hypertension (PH) associated with idiopathic pulmonary fibrosis (IPF). A retrospective analysis of functional status of cardiorespiratory system in 10 died patients with IPF (5 males and 5 females, the average age, 63.1 ± 9.2 yrs) was performed. During the last 6 months of their life, all the patients were investigated using body plethysmography, lung diffusing capacity test, arterial blood gas analysis and Doppler echocardiography measuring maximal systolic pulmonary artery (PA) pressure (sysPAP). We also performed histological examination of autopsy samples and morphometric examination of the PA and the heart. Severe restrictive disorders, significant decrease in the lung diffusing capacity with alveolo-capillary block and arterial hypoxemia have been found. The sysPAP was 44.9 ± 17.4 mm Hg in average. Microscopic lung tissue disorders were characteristic for usual interstitial pneumonia. Diameter of the pulmonary vessel lumen in IPF patients was 1.5-fold less and the vessel area was 1.7-fold less than those in controls. In IPF patients, the PA branch wall was 2.9-fold thicker, the proportion of the muscle area was 2.2-fold more and that of the intima area was 4.1-fold more than those in controls. Correlations were found between sysPAP and the cross-sectional area f the PA small branches (r = 0.71; p < 0.05), sysPAP and the proportion of intima area (r = 0.68, p < 0.05). Lumen diameter of the PA small branches correlated with the right atrium length (r = –0.81; p < 0.05) and the right ventricle mass correlated with diameter (r = –0.71; p < 0.05) and the cross-sectional area of the PA small branches (r = –0.75; p < 0.05). Significant correlations were also found between lung function, lung diffusing capacity and function signs of PH. Therefore, secondary PH in IPF is characterized by wall remodeling in the PA branches, mainly due to changes of intima. The 1.5-fold reduction of the vessel lumen is thought to be a cause of moderate growth of sysPAP followed by occurrence of cor pulmonale.

1. Costabel U., King T.E. International Consensus Statement on idiopathic pulmonary fibrosis. Eur. Respir. J. 2001; 17: 163–167.

2. American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment; international consensus statement-American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am. J. Respir. Crit. Care Med. 2000; 161: 646–664.

3. Hubbard R., Johnston I., Britton J. Survival in patients with cryptogenic fibrosing alveolitis: a population-based cohort study. Chest 1998; 113: 396–400.

4. Panos R.J., Mortenson R., Niccoli S.A., King T.E. Clinical deterioration in patients with idiopathic pulmonary fibrosis: causes and assessment. Am. J. Med. 1990; 88: 396–404.

5. Nathan S., Shlobin O., Ahmad S. et al. Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. Chest 2007; 131: 657–663.

6. Hopkins N., McLoughlin P. The structural basis of pulmonary hypertension in chronic lung disease: remodeling, rarefaction or angiogenesis? J. Anat. 2002; 201: 335–348.

7. Quanjer Ph.H., Tammeling G., Cotes J.E. et al. Lung volumes and forced ventilatory flows. Eur. Respir. J. 1993; 6 (suppl. 16): 5–40.

8. Cotes J.E., Chinn D.J., Quanjer Ph.H. et al. Standartization of the measurement of transfer factor (diffusing capacity). Eur. Respir. J. 1993; 6 (suppl. 16): 41–52.

9. Berger M., Haimovitz A., Van Tosh A. et al. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J. Am. Coll. Cardiol. 1985; 6: 359–365.

10. Kircher B., Himelman R.B., Schiller M.B. Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Am. J. Cardiol. 1990; 66 (4): 493–496.

11. Ильин Г.И. К вопросу о диагностике гипертрофии миокарда методом взвешивания. Арх. пат. 1956; 8: 97–101.

12. Voelkel N.F., Tuder R.M. Cellular and molecular mechanisms in the pathogenesis of severe pulmonary hypertension. Eur. Respir J. 1995; 8: 2129–2138.

13. Sawai T., Fujiyama J., Takahashi M., Takahashi T. The site of elevated vascular resistance in early paraquat lungs: a morphometric study of pulmonary arteries. Tohoku J. Exp. Med. 1994; 174 (2): 129–140.