1. Department of Cardio-Pulmonary Circulation 2. Department of Radiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China 3. Thrombosis and Vascular Medicine Center, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China
Pulmonary hypertension (PH), as a complication of bronchiectasis, is associated with increased mortality. However, hemodynamic characteristics and the efficacy of pulmonary arterial hypertension (PAH) therapies in patients with bronchiectasis and PH remain unknown. Patients with bilateral bronchiectasis and concurrent PH were included in the study. Patient characteristics at baseline and during follow-up, as well as survival, were analyzed. This observational study was conducted in 36 patients with a mean age of 51.5 years (range, 17?74 years). The 6 min walking distance was 300.8±93.3 m. The mean pulmonary arterial pressure (PAP) was 41.5±11.7 mmHg, cardiac output was 5.2±1.4 L/min, and pulmonary vascular resistance was 561.5±281.5 dyn·s·cm−5. The mean PAP was>35 mmHg in 75% of the cases. Mean PAP was inversely correlated with arterial oxygen saturation values (r = −0.45, P = 0.02). In 24 patients who received oral PAH therapy, systolic PAP was reduced from 82.4±27.0 mmHg to 65.5±20.9 mmHg (P = 0.025) on echocardiography after a median of 6 months of follow-up. The overall probability of survival was 97.1% at 1 year, 83.4% at 3 years, and 64.5% at 5 years. Given the results, we conclude that PH with severe hemodynamic impairment can occur in patients with bilateral bronchiectasis, and PAH therapy might improve hemodynamics in such patients. Prospective clinical trials focusing on this patient population are warranted.
History of right heart failure or lower limb edema (number [%])
26 (72.2)
10 (28.6)
<0.001
Syncope at exercise (number [%])
0 (0)
1 (2.8)
0.310
Finger clubbing (number [%])
18 (50.0)
3 (8.6)
<0.001
FEV1/FVC (%)
56.0±15.6
59.8±15.1
0.350
FEV1 (% pred., median [IQR])
27.5 (20.9–30.7)
36.7 (26.4–58.8)
0.009
TLC (% pred.)
112.3±18.9
110.0±27.7
0.740
DLco (% pred.)
39.4±18.7
69.2±34.5
0.011
PaCO2 (mmHg, median [IQR])
51.7 (46.5–58.7)
41.5 (38.4–43.9)
<0.001
PaO2 (mmHg)
57.8±14.0
78.6±17.6
<0.001
RA dimension (mm)
46.1±11.2
33.5±4.8
<0.001
RV dimension (mm)
43.2±9.2
29.7±4.6
<0.001
LVEF (%)
69.2±10.6
68.8±7.0
0.873
TRV (m/s)
4.0±0.6
2.5±0.3
<0.001
sPAP (mmHg)
70.6±21.4
31.3±6.2
<0.001
TAPSE (mm)
17.3±3.5
20.5±3.1
<0.001
RAP (mmHg)
7.9±3.9
6.0±1.5
0.015
Image type (number [%])
<0.001
Cystic bronchiectasis
15 (41.7)
9 (25.7)
Cylindrical bronchiectasis
3 (8.3)
16 (45.7)
Mixed bronchiectasis
18 (50.0)
10 (28.6)
Extent of bronchiectasis (median [IQR])
17.0 (16.0–17.8)
15.0 (11.0–17.0)
0.001
Six-minute walk distance (m)
300.8±93.3
401.2±89.7
0.001
NT-proBNP (pg/ml, median [IQR])
864.0 (517.0–1737.0)
96.0 (43.0-228.0)
0.005
Tab.1
Characteristic
No. of patients
Value
PVR (dyn·s·cm-5)
33
561.5±281.5
PAWP (mmHg)
33
8.7±3.5
sPAP (mmHg)
36
68.5±17.1
dPAP (mmHg)
36
23.3±8.8
mPAP (mmHg)
36
41.5±11.7
RAP (mmHg)
36
5.0±4.4
CO (L/min)
36
5.2±1.4
CI (L/(min•m2))
36
3.5±0.8
SvO2 (%)
33
59.1±9.7
MAP (mmHg)
36
90.8±19.8
Tab.2
Fig.2
Fig.3
Variables
No. of patients
Pretreatment
Post-treatment
P
LVEF (%)
24
70.6±15.1
69.3±11.1
0.692
TRV (m/s)
24
4.2±0.8
3.6±0.5
0.012
sPAP (mmHg)
24
82.4±27.0
65.5±20.9
0.025
TAPSE (mm)
24
15.7±2.2
18.3±4.5
0.063
RAP (mmHg)
24
8.9±3.7
8.5±2.8
0.773
NT-proBNP (pg/ml, median [IQR])
15
748.5 (351.8–1658.5)
504.0 (161.5–3016.5)
0.925
PaO2 (mmHg)
18
58.8±14.3
52.4±11.3
0.394
PaCO2 (mmHg)
18
52.5±8.2
51.5±9.5
0.175
SaO2 (%)
18
85.8±8.3
82.4±9.0
0.769
DA-aO2 (mmHg)
18
50.3±37.5
51.8±25.7
0.117
Tab.3
Fig.4
1
Alzeer AH, Al-Mobeirek AF, Al-Otair HA, Elzamzamy UA, Joherjy IA, Shaffi AS. Right and left ventricular function and pulmonary artery pressure in patients with bronchiectasis. Chest 2008; 133(2): 468–473
https://doi.org/10.1378/chest.07-1639
pmid: 18071019
Ip M, Lauder IJ, Wong WY, Lam WK, So SY. Multivariate analysis of factors affecting pulmonary function in bronchiectasis. Respiration 1993; 60(1): 45–50
https://doi.org/10.1159/000196172
pmid: 8469819
5
Ashour M. Hemodynamic alterations in bronchiectasis: a base for a new subclassification of the disease. J Thorac Cardiovasc Surg 1996; 112(2): 328–334
https://doi.org/10.1016/S0022-5223(96)70258-1
pmid: 8751499
6
Devaraj A, Wells AU, Meister MG, Loebinger MR, Wilson R, Hansell DM. Pulmonary hypertension in patients with bronchiectasis: prognostic significance of CT signs. AJR Am J Roentgenol 2011; 196(6): 1300–1304
https://doi.org/10.2214/AJR.10.5221
pmid: 21606292
Sugino K, Ota H, Fukasawa Y, Uekusa T, Homma S. Pathological characteristics in idiopathic nonspecific interstitial pneumonia with emphysema and pulmonary hypertension. Respirol Case Rep 2013; 1(2): 39–42
https://doi.org/10.1002/rcr2.18
pmid: 25473539
9
Quiñones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA; Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography.Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr 2002; 15(2): 167–184 PMID:11836492
https://doi.org/10.1067/mje.2002.120202
10
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 16(3):233–270 PMID: 25712077 DOI: 10.1093/ehjci/jev014
11
Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD, Louie EK, Schiller NB. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010; 23(7): 685–713; quiz 786–688 PMID: 20620859 DOI: 10.1016/j.echo.2010.05.010
12
Parent F, Bachir D, Inamo J, Lionnet F, Driss F, Loko G, Habibi A, Bennani S, Savale L, Adnot S, Maitre B, Yaïci A, Hajji L, O’Callaghan DS, Clerson P, Girot R, Galacteros F, Simonneau G. A hemodynamic study of pulmonary hypertension in sickle cell disease. N Engl J Med 2011; 365(1): 44–53
https://doi.org/10.1056/NEJMoa1005565
pmid: 21732836
13
Berger M, Haimowitz A, Van Tosh A, Berdoff RL, Goldberg E. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol 1985; 6(2): 359–365
https://doi.org/10.1016/S0735-1097(85)80172-8
pmid: 4019921
14
Lanzarini L, Fontana A, Lucca E, Campana C, Klersy C. Noninvasive estimation of both systolic and diastolic pulmonary artery pressure from Doppler analysis of tricuspid regurgitant velocity spectrum in patients with chronic heart failure. Am Heart J 2002; 144(6): 1087–1094
https://doi.org/10.1067/mhj.2002.126350
pmid: 12486435
15
Sitbon O, Humbert M, Jaïs X, Ioos V, Hamid AM, Provencher S, Garcia G, Parent F, Hervé P, Simonneau G. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation 2005; 111(23): 3105–3111
https://doi.org/10.1161/CIRCULATIONAHA.104.488486
pmid: 15939821
16
Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, Langleben D, Manes A, Satoh T, Torres F, Wilkins MR, Badesch DB. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol 2013; 62(25 Suppl): D42–D50
https://doi.org/10.1016/j.jacc.2013.10.032
pmid: 24355641
17
Jiang X, Wang YF, Zhao QH, Jiang R, Wu Y, Peng FH, Xu XQ, Wang L, He J, Jing ZC. Acute hemodynamic response of infused fasudil in patients with pulmonary arterial hypertension: a randomized, controlled, crossover study. Int J Cardiol 2014; 177(1): 61–65
https://doi.org/10.1016/j.ijcard.2014.09.101
pmid: 25499341
18
MacIntyre N, Crapo RO, Viegi G, Johnson DC, van der Grinten CP, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, Gustafsson P, Hankinson J, Jensen R, McKay R, Miller MR, Navajas D, Pedersen OF, Pellegrino R, Wanger J. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005; 26(4): 720–735
https://doi.org/10.1183/09031936.05.00034905
pmid: 16204605
19
Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J 2005; 26(2): 319–338 PMID:16055882
https://doi.org/10.1183/09031936.05.00034805
20
Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G. Standardisation of the measurement of lung volumes. Eur Respir J 2005; 26(3): 511–522
https://doi.org/10.1183/09031936.05.00035005
pmid: 16135736
21
Jo YS, Choi SM, Lee J, Park YS, Lee SM, Yim JJ, Yoo CG, Kim YW, Han SK, Lee CH. The relationship between chronic obstructive pulmonary disease and comorbidities: a cross-sectional study using data from KNHANES 2010–2012. Respir Med 2015; 109(1): 96–104
https://doi.org/10.1016/j.rmed.2014.10.015
pmid: 25434653
22
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1): 111–117
https://doi.org/10.1164/ajrccm.166.1.at1102
pmid: 12091180
23
Kim JS, Müller NL, Park CS, Grenier P, Herold CJ. Cylindrical bronchiectasis: diagnostic findings on thin-section CT. AJR Am J Roentgenol 1997; 168(3): 751–754
https://doi.org/10.2214/ajr.168.3.9057529
pmid: 9057529
Chaouat A, Bugnet AS, Kadaoui N, Schott R, Enache I, Ducoloné A, Ehrhart M, Kessler R, Weitzenblum E. Severe pulmonary hypertension and chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 172(2): 189–194
https://doi.org/10.1164/rccm.200401-006OC
pmid: 15831842
26
Andersen KH, Iversen M, Kjaergaard J, Mortensen J, Nielsen-Kudsk JE, Bendstrup E, Videbaek R, Carlsen J. Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease. J Heart Lung Transplant 2012; 31(4): 373–380
https://doi.org/10.1016/j.healun.2011.11.020
pmid: 22226804
27
Shorr AF, Wainright JL, Cors CS, Lettieri CJ, Nathan SD. Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant. Eur Respir J 2007; 30(4): 715–721
https://doi.org/10.1183/09031936.00107206
pmid: 17626111
28
Darke CS, Lewtas NA. Selective bronchial arteriography in the demonstration of abnormal systemic circulation in the lung. Clin Radiol 1968; 19(4): 357–367
https://doi.org/10.1016/S0009-9260(68)80074-1
pmid: 5716977
29
Datta G, Dastidar DG, Kundu S, Datta B, Dastidar NG, Bannerjee A. A case of primary ciliary dyskinesia with pulmonary arterial hypertension responding to oral sildenafil. J Assoc Physicians India 2011; 59: 738–740
pmid: 22616346
30
Daniil Z, Karetsi E, Zakynthinos E, Bakratsi E, Kalala F, Gourgoulianis KI. Pulmonary arterial hypertension in a patient with common variable immunodeficiency and unilateral bronchiectasis: successful treatment with iloprost. Eur J Intern Med 2007; 18(4): 333–335
https://doi.org/10.1016/j.ejim.2006.11.014
pmid: 17574112
31
Seeger W, Adir Y, Barberà JA, Champion H, Coghlan JG, Cottin V, De Marco T, Galiè N, Ghio S, Gibbs S, Martinez FJ, Semigran MJ, Simonneau G, Wells AU, Vachiéry JL. Pulmonary hypertension in chronic lung diseases. J Am Coll Cardiol 2013; 62(25 Suppl): D109–D116
https://doi.org/10.1016/j.jacc.2013.10.036
pmid: 24355635
32
Oswald-Mammosser M, Weitzenblum E, Quoix E, Moser G, Chaouat A, Charpentier C, Kessler R. Prognostic factors in COPD patients receiving long-term oxygen therapy. Importance of pulmonary artery pressure. Chest 1995; 107(5): 1193–1198
https://doi.org/10.1378/chest.107.5.1193
pmid: 7750305
33
Yock PG, Popp RL. Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation. Circulation 1984; 70(4): 657–662
https://doi.org/10.1161/01.CIR.70.4.657
pmid: 6478568
34
Currie PJ, Seward JB, Chan KL, Fyfe DA, Hagler DJ, Mair DD, Reeder GS, Nishimura RA, Tajik AJ. Continuous wave Doppler determination of right ventricular pressure: a simultaneous Doppler-catheterization study in 127 patients. J Am Coll Cardiol 1985; 6(4): 750–756
https://doi.org/10.1016/S0735-1097(85)80477-0
pmid: 4031289
35
Laaban JP, Diebold B, Zelinski R, Lafay M, Raffoul H, Rochemaure J. Noninvasive estimation of systolic pulmonary artery pressure using Doppler echocardiography in patients with chronic obstructive pulmonary disease. Chest 1989; 96(6): 1258–1262
https://doi.org/10.1378/chest.96.6.1258
pmid: 2582830
36
Arcasoy SM, Christie JD, Ferrari VA, Sutton MS, Zisman DA, Blumenthal NP, Pochettino A, Kotloff RM. Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. Am J Respir Crit Care Med 2003; 167(5): 735–740
https://doi.org/10.1164/rccm.200210-1130OC
pmid: 12480614
37
Fisher MR, Criner GJ, Fishman AP, Hassoun PM, Minai OA, Scharf SM, Fessler HE; NETT Research Group. Estimating pulmonary artery pressures by echocardiography in patients with emphysema. Eur Respir J 2007; 30(5): 914–921 PMID:17652313
https://doi.org/10.1183/09031936.00033007