dyspnea (NYHA functional class IV), and severe hypoxemia (PaO2 at 32 mmHg at ambient air), that couldn’t be fully explained by lung involvement. Echocardiography revealed elevated pulmonary pressures associated with dilated right heart chambers and a fattening of the interventricular septum. Brain natriuretic peptide was mildly elevated at 162 pg/mL (normal <80), and 6MWD was reduced to 396 m with desaturation from 82% to 72%. RHC was performed and revealed severe precapillary PH with mPAP, PAWP, CI, and PVR at 49 mmHg, 11 mmHg, 1.5 L/ min/m2, and 13.6 WU, respectively (Table 41.2). Speci c PAH therapies are classically not recommended apart from group 1 PH. However, it can be considered in experts centers, in case of severe PH [1]. Thereby, speci c combination PAH therapy associating an endothelin receptor antagonist and a phosphodiesterase type 5 inhibitor was sequentially and carefully introduced. Six months later, despite speci c PAH therapy, reassessment showed no clinical improvement (NYHA functional class III and decrease in 6MWD to 260 m), despite a mild hemodynamic improvement (mPAP 41 mmHg, CI 1.7 L/min/m2 and PVR 8.1 WU). To date, the bene t/risk ratio of PAH speci c therapies in this indication remains to be determined.

Table 41.2  Pulmonary function tests and hemodynamic assessment at time of PH diagnosis

CI cardiac index, DLCO diffusing capacity for carbon monoxide corrected for hemoglobin, FEV1 forced expiratory volume in 1 s, FVC forced vital capacity, mPAP mean pulmonary arterial pressure, PAWP pulmonary arterial wedge pressure, PVR pulmonary vascular resistance, RAP right atrial pressure, TLC total lung capacity, WU wood units

Box 41.1 Diagnostic Criteria for Severe PH

The diagnosis of PH is con rmed by right heart catheterization.

According to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension [1], precapillary PH is de ned by:

mPAP >20 mmHg

PAWP ≤ 15 mmHg

PVR ≥ 2 WU

In orphan lung diseases, “severe PH”:

  Was historically de ned by: mPAP >35 mmHg, and/or CI <2.5 L/min1/m2

Is currently de ned by: PVR >5 WU

CI cardiac index, mPAP mean pulmonary arterial pressure, PAWP pulmonary arterial wedge pressure, PH pulmonary hyper­ tension, PVR pulmonary vascular resistances, WU wood units

Fig. 41.6  HRCT of the chest showing a typical combined pulmonarybrosis and emphysema syndrome. 1-mm-thick frontal CT section depicting the presence of diffuse emphysema, associated with the presence of reticulation pattern, cystic lesions, and traction bronchiectasis with a predominance in the lower lobes and in the right lung

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