Hemodynamic and gas exchange effects of inhaled iloprost in patients with COPD and pulmonary hypertension

Figures & data

Table 1 Characteristics of the patients participating in the study

Characteristic	All patients, N=67	Nonsevere COPD-PH, N=30	Severe COPD-PH, N=37
Age, years	58.3 (12.1)	60.7 (12.5)	56.3 (11.6)
Men, %	40 (59.7)	22 (73.3)	18 (48.6)*
BMI, kg⋅m^−2	21.3 (4.8)	20.8 (3.3)	21.7 (5.7)
Echocardiography
Systolic PAP, mmHg	63.1 (23.9)	47.9 (17.0)	74.4 (22.0)**
LVEF, %	67.2 (9.5)	64.6 (7.7)	69.1 (10.3)
TAPSE, cm	17.6 (3.2)	18.6 (3.0)	17.1 (3.2)
Pulmonary function
TLC, %	101.7 (25.5)	97.1 (25.5)	105.2 (25.3)
FEV1/FVC, %	49.1 (11.1)	49.3 (10.9)	48.9 (11.4)
FEV1, %	31.4 (13.1)	32.4 (12.3)	30.7 (13.7)
RV, %	184.7 (63.4)	173.1 (72.5)	192.9 (55.9)
DLCO/VA, %	58.5 (31.1)	58.9 (31.1)	58.1 (32.0)

Notes:

* p<0.05 and

** p<0.01 compared with values for patients with nonsevere COPD-PH. Data shown are mean (standard deviation) or numbers of patients (men).

Abbreviations: BMI, body mass index; COPD-PH, pulmonary hypertension associated with COPD; DLCO/VA, diffusing capacity divided by the alveolar volume; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; LVEF, left ventricular ejection fraction; RV, residual volume; systolic PAP, systolic pulmonary arterial pressure; TAPSE, tricuspid annular plane systolic excursion; TLC, total lung capacity.

Table 2 Hemodynamic and gas exchange parameters in patients with COPD-PH before and after administration of iloprost

Parameter	N	Baseline, mean (SD)	After iloprost, mean (SD)	Change after iloprost, mean (95% CI)
PVR, dyn⋅s⋅cm^−5	67	491.9 (244.5)	429.6 (243.3)**	−62.4 (−92.9 to −31.8)
PAWP, mmHg	67	10.2 (3.5)	10.4 (3.6)	0.2 (−0.3 to 0.7)
mPAP, mmHg	67	39.6 (10.4)	37.4 (10.9)**	−2.1 (−3.3 to −1.0)
RAP, mmHg	67	7.2 (4.4)	7.5 (4.6)	0.4 (−0.1 to 0.8)
CIx, L⋅min^−1⋅m^−2	67	3.3 (0.9)	3.5 (0.9)**	0.2 (0.1 to 0.3)
CO, L⋅min^−1	67	5.2 (1.7)	5.6 (1.9)**	0.4 (0.2 to 0.5)
MAP, mmHg	67	97.0 (14.8)	95.1 (1.8)	−1.9 (−4.3 to 0.5)
PaO2, mmHg	60	59.4 (11.2)	59.3 (11.7)	0.1 (−1.8 to 2.0)
PaCO2, mmHg	60	51.1 (12.1)	51.2 (13.1)	−0.01 (−1.7 to 1.7)
SaO2, %	60	87.5 (6.1)	87.2 (6.4)	−0.3 (−1.4 to 0.9)
DA − aO2, mmHg	60	27.5 (14.3)	28.6 (11.6)	1.1 (−1.6 to 3.8)
Qs/Qt, %	60	14.9 (6.6)	15.6 (5.3)	0.7 (−0.5 to 2.0)

Note:

** p<0.01 compared with pretreatment values.

Abbreviations: CIx, cardiac index; CO, cardiac output; COPD-PH, pulmonary hypertension associated with COPD; D_A − _aO_2, alveolar–arterial oxygen partial pressure difference; MAP, mean atrial pressure; mPAP, mean pulmonary arterial pressure; PaCO_2, partial pressure of carbon dioxide in arterial blood; PaO_2, partial pressure of oxygen in arterial blood; PAWP, pulmonary arterial wedge pressure; PVR, pulmonary vascular resistance; Qs/Qt, pulmonary shunt ratio; RAP, right atrial pressure; SaO_2, arterial oxygen saturation.

Table 3 Hemodynamic and gas exchange parameters in patients with severe or nonsevere COPD-PH before and after administration of iloprost

Parameter	Nonsevere COPD-PH			Severe COPD-PH
	n	Baseline, mean (SD)	Change after iloprost, mean (95% CI)	n	Baseline, mean (SD)	Change after iloprost, mean (95% CI)
PVR, dyn⋅s⋅cm^−5	30	317.9 (111.3)	−27.4 (−49.9 to −4.8)*	37	628.3 (234.1)**	−89.7 (−140.7 to −38.8)*,a
PAWP, mmHg	30	10.2 (2.9)	0.2 (−0.4 to 0.7)	37	9.7 (3.7)	0.2 (−0.5 to 1.0)
mPAP, mmHg	30	30.6 (3.3)	−1.0 (−2.1 to 0.1)	37	46.8 (8.4)**	−3.1 (−5.0 to 1.1)*
RAP, mmHg	30	5.6 (2.7)	0.8 (0.3 to 1.4)*	37	7.4 (4.8)	−0.03 (−0.7 to 0.7)a
CO, L⋅min^−1	30	5.4 (1.7)	0.2 (0.1 to 0.6)	37	5.1 (1.7)	0.6 (0.3 to 0.7)*
CIx, L⋅min^−1⋅m^−2	30	3.4 (0.9)	0.2 (0.1 to 0.6)	37	3.2 (0.9)	0.3 (0.2 to 0.4)*
MAP, mmHg	30	99.2 (16.0)	−1.6 (−5.8 to 3.1)	37	93.9 (13.1)	−2.4 (−5.0 to 0.2)
PaO2, mmHg	25	65.0 (11.7)	2.3 (−1.4 to 6.1)	35	55.5 (9.4)***	−0.9 (−3.5 to 1.8)
PaCO2, mmHg	25	50.1 (9.6)	−0.7 (−4.0 to 2.5)	35	51.9 (13.5)	0.8 (−1.2 to 2.8)
SaO2, %	25	90.5 (5.1)	0.01 (−1.13 to 1.15)	35	85.4 (5.9)***	−0.5 (−2.3 to 1.3)
DA − aO2, mmHg	25	22.5 (10.3)	2.8 (−0.9 to 6.5)	35	31.1 (15.6)**	−0.07 (−4.1 to 3.9)
Qs/Qt, %	25	12.7 (5.2)	1.4 (−0.4 to 3.2)	35	16.5 (7.0)**	0.2 (−1.5 to 2.0)

Notes:

* p<0.05 compared with baseline values.

** p<0.05 and

*** p<0.01 compared with corresponding values for patients with nonsevere COPD-PH.

a p<0.05 compared with change for patients with nonsevere COPD-PH.

Abbreviations: CIx, cardiac index; CO, cardiac output; COPD-PH, pulmonary hypertension associated with COPD; D_A − _aO₂, alveolar–arterial oxygen partial pressure difference; MAP, mean atrial pressure; mPAP, mean pulmonary arterial pressure; PaCO₂, partial pressure of carbon dioxide in arterial blood; PaO₂, partial pressure of oxygen in arterial blood; PAWP, pulmonary arterial wedge pressure; PVR, pulmonary vascular resistance; Qs/Qt, pulmonary shunt ratio; RAP, right atrial pressure; SaO₂, arterial oxygen saturation.

Figure 1 Effects of iloprost administration on pulmonary hemodynamics.

Notes: Top: for patients with nonsevere and severe COPD-PH, hemodynamic parameters before (open columns) and after (solid columns) iloprost treatment: (A) mPAP, (B) CO, and (C) PVR. Bottom: magnitude of changes induced by iloprost treatment in (D) mPAP and (E) PVR. Values presented as mean ± standard error. *p<0.05 compared with pretreatment values. **p<0.05 compared with corresponding values for patients with nonsevere COPD-PH. ***p<0.05 compared with change for patients with nonsevere COPD-PH.
Abbreviations: CO, cardiac output; COPD-PH, pulmonary hypertension associated with COPD; mPAP, mean pulmonary arterial pressure; PVR, pulmonary vascular resistance.

Figure 2 Effects of iloprost administration on gas exchange.

Notes: Top: for patients with nonsevere and severe COPD-PH, gas exchange before (open columns) and after (solid columns) iloprost treatment: (A) PaO₂, (B) D_A − _aO₂, and (C) Qs/Qt. Bottom: magnitude of changes induced by iloprost administration in (D) PaO₂ and (E) D_A − _aO₂. Values presented as mean ± standard error. *p<0.05 and **p<0.01 compared with corresponding values for patients with nonsevere COPD-PH.
Abbreviations: COPD-PH, pulmonary hypertension associated with COPD; D_A − _aO₂, alveolar–arterial oxygen partial pressure difference; PaO₂, partial pressure of oxygen in arterial blood; Qs/Qt, pulmonary shunt ratio.

Figure 3 Relationship between baseline PaO₂ values and the changes in (A) PaO₂, (B) Qs/Qt, and (C) D_A − _aO₂ following administration of iloprost to patients with severe COPD-PH.

Abbreviations: COPD-PH, pulmonary hypertension associated with COPD; D_A − _aO₂, alveolar–arterial oxygen partial pressure difference; PaO₂, partial pressure of oxygen in arterial blood; Qs/Qt, pulmonary shunt ratio.