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Review article

Interstitial lung diseases and secondary pulmonary hypertension

Slobodan Belić1, Nikola Marić1, Nataša Đurđević1, Aleksa Golubović1, Ivan Milivojević1, Miloš Geratović1, Nikola Nikolić1, Irina Čokrlić1, Mihailo Stjepanović1,2
  • University Clinical Center of Serbia, Clinic for Pulmonology, Belgrade, Serbia
  • University of Belgrade, Faculty of Medicine, Belgrade, Serbia

ABSTRACT

Interstitial lung disease alone can have a poor prognosis, and when associated with pulmonary hypertension there is a significant reduction in survival rates. Since the incidence of pulmonary hypertension in patients with interstitial lung diseases is very high and the symptoms are similar and often unrecognized, our aim is to point out the significance of both coexisting diseases and to prompt clinicians to suspect pulmonary hypertension. Through a brief review of the pathohistological changes, diagnostic methods, and the clinical presentation of these diseases, the similarities and differences that can help in the management of these patients, are shown. The latest treatment guidelines, with a special focus on the impact of antifibrotic treatment (nintedanib and pirfenidone) on pulmonary hypertension, are presented.


INTRODUCTION

Interstitial lung disease (ILD) is an umbrella term for a group of diverse pulmonary diseases characterized by similar radiographic and clinical manifestations, as well as similar pathological changes in the lung parenchyma. The term interstitial disease indicates that all of these conditions initially originate from the lung parenchyma, however, in most of these diseases there is also extensive damage to the alveolar architecture as well as to the airways themselves. The interstitium is the area inside and around the alveolar walls, where, in fact, gas exchange occurs [1],[2].

These diseases are primarily categorized as those with a known cause and idiopathic diseases. Also, they can be categorized as those with a genetic predisposition (less than 20%) and acquired diseases [3]. In approximately one third of the patients, we know that the disease is caused by the effect of environmental agents (hypersensitive pneumonitis, pneumoconioses, drug-induced diseases, diseases caused by radiation, postinfectious diseases – bacteria, viruses, mycoses), while in the remaining two thirds of the patients the cause is unknown (sarcoidosis, idiopathic interstitial pneumonia, interstitial diseases within systemic connective tissue disorders, etc.). Idiopathic interstitial pneumonia is further classified as: idiopathic pulmonary fibrosis (IPF) with usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), interstitial lung disease with respiratory bronchitis, desquamative interstitial pneumonia (DIP), cryptogenic organizing pneumonia (COP), lymphoid interstitial pneumonia (LIP), and acute interstitial pneumonia (AIP) [4]. The epidemiology is not quite precise due to difficulty in establishing the diagnosis. Some countries have a registry of these diseases, however, the issue remains as to the validity of these registries, as the data are quite contradictory. According to available data, the most frequent interstitial diseases are sarcoidosis and idiopathic pulmonary fibrosis (they account for over 50% of ILDs) [5].

DIAGNOSTICS

The complaints that these patients report to the doctor are nonspecific, most commonly these are fatigue, non-productive cough, and difficulty breathing. These are particularly pronounced during physical activity, and they become progressively worse. Frequently, these complaints are not even recognized in patients with associated diseases (such as cardiological patients, patients with systemic connective tissue disorders, patients with other pulmonary diseases). In order to reach the correct diagnosis on time, anamnestic data must always be recorded correctly (attention must be given to the existence of occupational diseases, other associated diseases), a clinical examination must be performed, respiratory function tests must be carried out, as well as a chest X-ray (examination of current and previous X-ray images, if they are available, is necessary), and high-resolution computed tomography (HRCT) of the chest, and, if needed, bronchological examination with analysis of the bronchial aspirate, the bronchoalveolar lavage fluid (BALF), or of the tissue itself. In some clinical situations, even more invasive diagnostic methods are indicated, such as surgical lung biopsy.

Regardless of the cause of the development of interstitial diseases, there is always a factor provoking a response in a sensitive host. First, an inflammatory process develops in the alveolar wall, the interstitium, and the terminal bronchioles, followed by connective tissue proliferation, altering the pulmonary microarchitecture, thus leading to irreversible fibrosis. As the result of the progression of interstitial lung disease, respiratory insufficiency, secondary pulmonary infections, as well as secondary pulmonary hypertension develop [6],[7].

PULMONARY HYPERTENSION

Pulmonary hypertension (PH) is a pathophysiological disorder which may encompass a number of clinical conditions and may be linked to different cardiovascular and pulmonary diseases. It is defined as the elevation of pulmonary arterial pressure (PAP) ≥ 20 mmHg at rest, which we assess with right heart catheterization. The term pulmonary arterial hypertension (PAH) describes a group of patients with pulmonary hypertension who are hemodynamically characterized by the presence of precapillary PH, defined by pulmonary artery wedge pressure (PAWP) 15 mmHg and pulmonary vascular resistance (PVR) > 2 Wood units [8].

In recent years, significant progress in the diagnostics and treatment of pulmonary hypertension has been made, and the definition of this disease was amended, in the sense that the cut-off levels of PAP and PVR were revised, in the 2022 ESC/ERS1 Guidelines for the diagnosis and treatment of pulmonary hypertension. According to the World Health Organization, the causes of pulmonary hypertension are categorized into five groups (based on the etiology of their development). In the registries, half of the pulmonary arterial hypertensions belong to the idiopathic, hereditary, and drug-induced groups; in the group of conditions associated with PAH, the most common cause are connective tissue diseases (with a dominance of systemic sclerosis) [9]. The severe form of PAH can be verified in combined pulmonary fibrosis and emphysema syndrome, where the prevalence of the disease is high.

1 European Society of Cardiology/European Respiratory Society

THE EFFECT OF PULMONARY FIBROSIS ON THE DEVELOPMENT OF PULMONARY HYPERTENSION

The basic pathophysiological mechanism of the development of pulmonary hypertension in patients with ILD is pulmonary vasoconstriction resulting from a decreased quantity of oxygen and the anatomical reduction of the pulmonary vascular bed [10]. As a response to this condition, a proliferation of endothelial cells, smooth muscle cells, and fibroblasts occurs, together with a hypertrophy of the media and adventitia. All layers of the pulmonary arteries exhibit concentric and eccentric remodeling; a widely distributed hyperplasia of the intima is the result of the presence of endothelial cells, while in the media and the adventitia there is a thickening which is the result of hypertrophy and/or hyperplasia of the smooth muscle cells and fibroblasts. Longitudinally oriented smooth muscle cells can be seen in the media, which is characteristic of hypoxic pulmonary hypertension. The capillary network is, in the parts of the lungs that are infiltrated with fibrosis, reduced, while the space between the capillaries and the basement membrane is increased. In the veins, the adventitia thickens, smooth muscle cell hyperplasia occurs, the lumen occludes, fibrosis of the intima develops, and the elastic lamina thickens [11]. All of these changes to the blood vessels may be present in patients with ILD, regardless of whether pulmonary hypertension is present as well, however, they are more frequent in patients with both diseases [12]. In patients with pulmonary fibrosis, morphological changes in the vascular network develop independently of the cause, while remodeling is present in all types of blood vessels throughout the lungs. The blood vessel lumen becomes progressively narrower. The end result of these changes is permanent increase of pulmonary vascular resistance, i.e., the development of chronic pulmonary hypertension [13]. However, many clinical studies that have been carried out did not find any correlation between the extent of pulmonary fibrosis and PAP, measured with high resolution computed tomography of the thorax. Therefore, damage to the lung tissue and the development of scar tissue does not explain the development of pulmonary hypertension in patients with ILD [14].

The first symptoms that occur in patients with pulmonary hypertension are also nonspecific and are very similar to those occurring in patients with interstitial lung disease, with the dominant ones being dyspnea on exertion and progressive fatigue, which become more pronounced with time, until a more severe form of pulmonary hypertension develops with all the signs of right ventricular weakness/failure (middle chest pain, syncope with exertion, body weight increase due to fluid retention, the development of ascites, abdominal pain due to liver congestion, etc.). The symptoms are often unrecognized, especially in the groups of older patients, in patients with a deteriorating general health status, and in those with a number of comorbidities [15]. According to some statistical data, over 20 % of patients have symptoms of pulmonary hypertension for longer than 24 months before the diagnosis is established [16].

DIAGNOSTICS OF PULMONARY HYPERTENSION

Pulmonary hypertension is a frequent comorbidity in patients with interstitial pulmonary disease, however, as mentioned previously, the diagnosis is more difficult to establish due to nonspecific symptoms. The golden standard is right heart catheterization, although the procedure is invasive and expensive. It is still not performed routinely in patients with ILD (except within preparations for lung transplantation). However, significant effort is being made to find a reliable noninvasive method that would make it easier to establish the diagnosis of pulmonary hypertension in these patients [17].

In patients with ILD, respiratory function tests are used for assessing the degree of lung damage. Forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) are two indicators of pulmonary function of the greatest interest. Both parameters are reduced in patients with ILD and they correlate with the progression of disease. DLCO is a parameter which may be decreased in patients with pulmonary hypertension, without the presence of interstitial lung disease in these patients [18]. Therefore, any decrease of the DLCO value which is not proportionate to the degree of pulmonary fibrosis may be the sign of associated pulmonary arterial hypertension. Zisman et al. developed a mathematical formula which predicts the value of PAP, by using FVC, DLCO, and oxygen saturation [18], and the precision of this formula has been confirmed in two studies, but with a small number of patients with IPF, which is why confirmation is necessary on a larger group of subjects, in order to validate the formula. Since the decrease of DLCO (the most common parameter of respiratory function deviating from normal values in patients with PAH) is not a specific sign (we find it in emphysema, chronic pulmonary embolism, pulmonary edema, anemia), the conclusion is that testing respiratory function alone has limited predictive value for discovering pulmonary arterial hypertension in patients with pulmonary fibrosis [19].

Ultrasound of the heart is, at present, the most commonly applied noninvasive diagnostic technique for screening patients with pulmonary hypertension, however, in patients with advanced lung disease, this method has limited accuracy for early detection of pulmonary hypertension. In a study involving 374 patients who were being prepared for lung transplantation, a group of authors discovered that the application of ultrasound for discovering pulmonary hypertension in patients with obstructive and interstitial pulmonary diseases was possible in only 44% of the cases, while in 52% of patients of this group the measured value of pulmonary hypertension was incorrect [20]. The existence of a poor ‘echosonographic window’ in patients with pulmonary disease also has a significant impact on these results.

High resolution computed tomography (HRCT) is used for diagnostic purposes in patients with ILD, but it may also be used for discovering pulmonary hypertension by assessing the dimensions of the pulmonary artery. Several studies have been carried out yielding conflicting results. In a study involving 30 patients with ILD, Devaraj et al. showed that there is no significant correlation between the diameter of the pulmonary artery and the value of PAP or PVR, measured with right heart catheterization [21], while Chin et al. demonstrated a correlation between the pulmonary artery diameter and PAP, in a much larger study, which included 101 patients. However, widening of the pulmonary artery can be found in patients with IPF, who do not have pulmonary hypertension, which limits the application of this method. This is why it has been proposed that the increase in the diameter of segmental arteries (three of the four segmental arteries need to have an increased diameter in order for the finding to indicate PH) should be taken as an indirect indicator of pulmonary hypertension [22].

As to other noninvasive methods, ergospirometry may be very useful. Several studies have shown that the parameters which are followed during the test as well as their proportion (minute ventilation, CO2 production, partial pressure of carbon dioxide) may show, not only the existence of pulmonary hypertension in patients with ILD, but also its severity [23]. Magnetic resonance imaging of the heart did not reveal any advantage, as compared to HRCT of the thorax, in the diagnosis of pulmonary hypertension, and the method is significantly more expensive and less accessible to patients. Finally, when all is analyzed, there still is no single noninvasive method that can verify the existence of pulmonary hypertension with great precision, however, the application of the said methods may lead the clinician to first suspect PH, and then confirm the diagnosis with right heart catheterization.

THERAPY

The patients with these two comorbidities have a very poor prognosis, and secondary pulmonary hypertension, which has a high prevalence in patients with ILD, is a significant predictor of mortality [24]. According to the data from literature, there is as yet no significant progress in the treatment of the third group of patients with pulmonary hypertension. Primarily, treatment of the underlying disease is performed, attempting to reduce hypoxia, which is the cause of pulmonary hypertension. As to supportive therapy, regular physical exercise is recommended, as well as respiratory rehabilitation, smoking cessation, and regular seasonal vaccination [25]. Introducing continuous oxygen therapy is indicated only in patients in whom chronic respiratory insufficiency is verified [26]. There is no proof that anticoagulation therapy is beneficial to these patients [27].

As to specific therapy, the patients were divided into two groups, those with the mild and the moderately severe forms, and those with the severe form of pulmonary hypertension. Only supportive therapy is recommended for the first group of patients, together with regular follow-up, every 6 to 12 months. Patients in the second group, i.e., those with the severe form of pulmonary hypertension (echocardiographically assessed right ventricular systolic pressure – RVSP > 60 mmHg or mPAP > 35 mmHg assessed with right heart catheterization), are generally treated with supportive therapy, while a smaller percentage of them receive specific therapy [27]. When supportive therapy brings no benefit to the patients belonging to the highly functioning group (according to the World Health Organization classification), we opt for applying specific treatment [28]. The drugs applied belong to the group of prostacyclin agonists (iloprost, treprostinil, epoprostenol, selexipag), inhibitors of phosphodiesterase type 5 (sildenafil, tadalafil), and soluble guanylate cyclase stimulators (riociguat). These drugs have proven efficacy in treating patients belonging to the first group, while in the third group (where ILD patients belong), their application is limited, and in some situations, it may even be harmful. Apart from treprostinil inhalations, no other drug has been approved for treating pulmonary hypertension in this group of patients [29]. The negative effect of drugs may be the result of their vasodilatory effect, which worsens the ventilation-perfusion ratio, which further worsens gas exchange that is already damaged in patients suffering from pulmonary disease. The drugs belonging to the group of endothelin receptor antagonists, such as ambrisentan, did not prove efficient and have been connected with frequent adverse effects (drop in oxygen saturation, progression of the underlying disease, frequent hospitalizations) [30].

Lung transplantation may be an option in patients belonging to the third group, in whom their condition deteriorates despite treatment. The effect of pulmonary hypertension on the transplantation outcome is uncertain. Several studies suggest that there is no negative effect of pulmonary hypertension on survival in patients with ILD who had undergone transplantation. However, some studies show that PH is a risk factor for ninety-day mortality after transplantation of a lung, and that PH may pose a higher risk for primary graft dysfunction [31].

Nintedanib and pirfenidone are the only two drugs with an antifibrotic effect which are officially listed in the guidelines for treating idiopathic pulmonary fibrosis. Nintedanib has broader indications for use in autoimmune interstitial lung diseases and in ILD within systemic connective tissue diseases, and as of 2014, it has officially been approved for IPF treatment [32]. Little is known on how these two drugs affect the pulmonary vascular network. Nintedanib is an inhibitor of tyrosine kinase which binds to growth factor receptors, and which plays an important role in both diseases. Two large, randomized studies have shown that nintedanib slows down the reduction of FVC in patients with IPF [33]. There are limited data on the effect of nintedanib on the pulmonary vascular network and on right ventricular remodeling. Research conducted on mice, in which changes to the lung parenchyma consistent with those occurring in systemic necrosis were induced, showed that the application of nintedanib did not only improve the histological characteristics of pulmonary fibrosis but also the anomalies in the blood vessels. In later reports, it was demonstrated that the drug did not prevent the remodeling of small blood vessels, however, it did not reduce the right ventricular systolic pressure either. Follow-up was performed in patients with pulmonary hypertension (small group) which were treated with nintedanib, and the results showed a deterioration of PVR and of the cardiac output [34]. Pirfenidone is applied in the treatment of IPF, and research assessing the combined therapy with pirfenidone and sildenafil in patients with IPF and a high risk of pulmonary hypertension is ongoing. In animal studies, the protective role of pirfenidone in the remodeling of the pulmonary vascular network was registered [35].

CONCLUSION

The coexistence of ILD (IPF) and PH renders the diagnostic and therapeutic approach more complex. Antifibrotics act by slowing down the progression of fibrosis, by decreasing the number of exacerbations of the disease, and by improving the quality of life of the patients. Research regarding the effect of antifibrotics on the vascular network of the lungs is ongoing. When both diseases are present, therapeutic options are limited with regards to pulmonary hypertension. In a retrospective study, median survival for patients with IPF was 23 months, while median survival in patients with IPF and pulmonary hypertension was only 11 months [36]. Pulmonary hypertension, when it develops due to hypoxia, is progressive and is associated with increased morbidity and mortality.

Bearing in mind all that has been said, the opinion of the authors of this article is that the possibility of pulmonary hypertension should always be considered in patients with interstitial lung disease, and all necessary diagnostic procedures should be carried out in order to determine the existence of the disease and then further monitor the course of the disease. Timely supportive therapy may make the everyday life of patients easier, while by carrying out clinical studies in this very group of patients we may expect to discover effective targeted therapy.

  • Conflict of interest:
    None declared.

Informations

Volume 4 No 1

March 2023

Pages 65-74
  • Keywords:
    antifibrotic treatment, nintedanib, pirfenidone, pulmonary hypertension
  • Received:
    12 November 2022
  • Revised:
    10 January 2023
  • Accepted:
    27 January 2023
  • Online first:
    25 March 2023
  • DOI:
  • Cite this article:
    Belić S, Marić N, Đurđević N, Golubović A, Milivojević I, Geratović M, et al. Interstitial lung diseases and secondary pulmonary hypertension. Serbian Journal of the Medical Chamber. 2023;4(1):65-74. doi: 10.5937/smclk4-41136
Corresponding author

Slobodan Belić
University Clinical Center of Serbia, Clinic for Pulmonology
2 Pasterova Street, 11000 Belgrade, Serbia
E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.


  • 1. Esposito DB, Lanes S, Donneyong M, Holick CN, Lasky JA, Lederer D, et al. Idiopathic Pulmonary Fibrosis in United States Automated Claims. Incidence, Prevalence, and Algorithm Validation. Am J Respir Crit Care Med. 2015 Nov 15;192(10):1200-7. doi: 10.1164/rccm.201504-0818OC. [CROSSREF]

    2. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al.; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68. doi: 10.1164/rccm.201807-1255ST. [CROSSREF]

    3. Fukihara J, Kondoh Y, Brown KK, Kimura T, Kataoka K, Matsuda T, et al. Probable usual interstitial pneumonia pattern on chest CT: is it sufficient for a diagnosis of idiopathic pulmonary fibrosis? Eur Respir J. 2020 Apr 9;55(4):1802465. doi: 10.1183/13993003.02465-2018. [CROSSREF]

    4. Stjepanović M, Belić S, Buha I, Marić N, Baralić M, Mihailović-Vučinić V. Rapidly progressive pulmonary fibrosis in COVID-19 pneumonia. Srp Arh Celok Lek 2021. 149(7-8): 467–470.

    5. Stankovic S, Stjepanovic M, Asanin M. Biomarkers in Idiopathic Pulmonary Fibrosis. Idiopathic Pulmonary Fibrosis. [Internet]. London: IntechOpen; 2021. [pristupljeno: novembar 2022.]. [HTTP]

    6. Bennett D, Mazzei MA, Squitieri NC, Bargagli E, Refini RM, Fossi A, et al. Familial pulmonary fibrosis: Clinical and radiological characteristics and progression analysis in different high resolution-CT patterns. Respir Med. 2017 May;126:75-83. doi: 10.1016/j.rmed.2017.03.020. [CROSSREF]

    7. Abramson MJ, Murambadoro T, Alif SM, Benke GP, Dharmage SC, Glaspole I; Australian IPF Registry. Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Australia: case-control study. Thorax. 2020 Oct;75(10):864-869. doi: 10.1136/thoraxjnl-2019-214478. [CROSSREF]

    8. Frost A, Badesch D, Gibbs JSR, Gopalan D, Khanna D, Manes A, et al. Diagnosis of pulmonary hypertension. Eur Respir J. 2019 Jan 24;53(1):1801904. doi: 10.1183/13993003.01904-2018. [CROSSREF]

    9. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237. [CROSSREF]

    10. Nathan SD, Barbera JA, Gaine SP, Harari S, Martinez FJ, Olschewski H, et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J. 2019 Jan 24;53(1):1801914. doi: 10.1183/13993003.01914-2018. [CROSSREF]

    11. Raghu G, Nathan SD, Behr J, Brown KK, Egan JJ, Kawut SM, et al. Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction. Eur Respir J. 2015 Nov;46(5):1370-7. doi: 10.1183/13993003.01537-2014. [CROSSREF]

    12. Đurđević N, Belić S, Stjepanović M, Ašanin M. Plućna hipertenzija u hroničnoj opstruktivnoj bolesti pluća. Odabrana poglavlja u pulmologjji. Beograd. Medicinski fakultet u Beogradu, 2023.

    13. Shorr AF, Wainright JL, Cors CS, Lettieri CJ, Nathan SD. Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant. Eur Respir J. 2007 Oct;30(4):715-21. doi: 10.1183/09031936.00107206. [CROSSREF]

    14. Nathan SD, Shlobin OA, Ahmad S, Urbanek S, Barnett SD. Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. Chest. 2007 Mar;131(3):657-663. doi: 10.1378/chest.06-2485. [CROSSREF]

    15. Mauban JR, Remillard CV, Yuan JX. Hypoxic pulmonary vasoconstriction: role of ion channels. J Appl Physiol (1985). 2005 Jan;98(1):415-20. doi: 10.1152/japplphysiol.00732.2004. [CROSSREF]

    16. Huitema MP, Bakker ALM, Mager JJ, Rensing BJWM, Smits F, Snijder RJ, et al. Prevalence of pulmonary hypertension in pulmonary sarcoidosis: the first large European prospective study. Eur Respir J. 2019 Oct 31;54(4):1900897. doi: 10.1183/13993003.00897-2019. [CROSSREF]

    17. Remy-Jardin M, Ryerson CJ, Schiebler ML, Leung ANC, Wild JM, Hoeper MM, et al. Imaging of Pulmonary Hypertension in Adults: A Position Paper from the Fleischner Society. Radiology. 2021 Mar;298(3):531-549. doi: 10.1148/ radiol.2020203108. [CROSSREF]

    18. Ghio S, Mercurio V, Fortuni F, Forfia PR, Gall H, Ghofrani A; TAPSE in PAH investigators. A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension. Eur Respir J. 2020 Sep 24;56(3):2000513. doi: 10.1183/13993003.00513-2020. [CROSSREF]

    19. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019 Jan 24;53(1):1801913. doi: 10.1183/13993003.01913-2018. [CROSSREF]

    20. Hemnes AR, Opotowsky AR, Assad TR, Xu M, Doss LN, Farber-Eger E, et al. Features Associated With Discordance Between Pulmonary Arterial Wedge Pressure and Left Ventricular End Diastolic Pressure in Clinical Practice: Implications for Pulmonary Hypertension Classification. Chest. 2018 Nov;154(5):1099-1107. doi: 10.1016/j.chest.2018.08.1033. [CROSSREF]

    21. Herve P, Lau EM, Sitbon O, Savale L, Montani D, Godinas L, et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J. 2015 Sep;46(3):728-37. doi: 10.1183/09031936.00021915. [CROSSREF]

    22. Esfandiari S, Wolsk E, Granton D, Azevedo L, Valle FH, Gustafsson F, et al. Pulmonary Arterial Wedge Pressure at Rest and During Exercise in Healthy Adults: A Systematic Review and Meta-analysis. J Card Fail. 2019 Feb;25(2):114-122. doi: 10.1016/j.cardfail.2018.10.009. [CROSSREF]

    23. Brownell R, Moua T, Henry TS, Elicker BM, White D, Vittinghoff E, et al. The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia. Thorax. 2017 May;72(5):424-429. doi: 10.1136/thoraxjnl-2016-209671. [CROSSREF]

    24. Belić S, Đurđević N, Stjepanović M, Ašanin M. Terapija plućne arterijske hipertenzije. Odabrana poglavlja u pulmologjji. Beograd. Medicinski fakultet u Beogradu, 2023.

    25. Galiè N, Channick RN, Frantz RP, Grünig E, Jing ZC, Moiseeva O, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019 Jan 24;53(1):1801889. doi: 10.1183/13993003.01889-2018. [CROSSREF]

    26. Benza RL, Gomberg-Maitland M, Elliott CG, Farber HW, Foreman AJ, Frost AE, et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest. 2019 Aug;156(2):323-337. doi: 10.1016/j.chest.2019.02.004. [CROSSREF]

    27. Hoeper MM, Kramer T, Pan Z, Eichstaedt CA, Spiesshoefer J, Benjamin N, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017 Aug 3;50(2):1700740. doi: 10.1183/13993003.00740-2017. [CROSSREF]

    28. Hoeper MM, Pausch C, Olsson KM, Huscher D, Pittrow D, Grünig E, et al. COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur Respir J. 2022 Jul 7;60(1):2102311. doi: 10.1183/13993003.02311-2021. [CROSSREF]

    29. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 Sep 30;351(14):1425-36. doi: 10.1056/NEJMra040291. [CROSSREF]

    30. Shapiro S, Torres F, Feldman J, Keogh A, Allard M, Blair C, et al. Clinical and hemodynamic improvements after adding ambrisentan to background PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a suboptimal therapeutic response (ATHENA-1). Respir Med. 2017 May;126:84- 92. doi: 10.1016/j.rmed.2017.03.025. [CROSSREF]

    31. Wardle AJ, Seager MJ, Wardle R, Tulloh RM, Gibbs JS. Guanylate cyclase stimulators for pulmonary hypertension. Cochrane Database Syst Rev. 2016 Aug 2;2016(8):CD011205. doi: 10.1002/14651858.CD011205.pub2. [CROSSREF]

    32. Simonneau G, Channick RN, Delcroix M, Galiè N, Ghofrani HA, Jansa P, et al. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN. Eur Respir J. 2015 Dec;46(6):1711-20. doi: 10.1183/13993003.00364-2015. [CROSSREF]

    33. Rubin LJ, Galiè N, Grimminger F, Grünig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. 2015 May;45(5):1303-13. doi: 10.1183/09031936.00090614. [CROSSREF]

    34. Ghofrani HA, Grimminger F, Grünig E, Huang Y, Jansa P, Jing ZC, et al. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial. Lancet Respir Med. 2016 May;4(5):361-71. doi: 10.1016/S2213-2600(16)30019-4. [CROSSREF]

    35. Poštić A, Stjepanović M, Marić N, Belić S, Dimić-Janjić S, Đurđević N, et al Značaj KL-6 u dijagnosticii i prognozi intersticijumskih bolesti pluća. Acta Clinica 2021; 2(1): 35-44.

    36. Rajagopal K, Bryant AJ, Sahay S, Wareing N, Zhou Y, Pandit LM, et al. Idiopathic pulmonary fibrosis and pulmonary hypertension: Heracles meets the Hydra. Br J Pharmacol. 2021 Jan;178(1):172-186. doi: 10.1111/bph.15036. [CROSSREF]


REFERENCES

1. Esposito DB, Lanes S, Donneyong M, Holick CN, Lasky JA, Lederer D, et al. Idiopathic Pulmonary Fibrosis in United States Automated Claims. Incidence, Prevalence, and Algorithm Validation. Am J Respir Crit Care Med. 2015 Nov 15;192(10):1200-7. doi: 10.1164/rccm.201504-0818OC. [CROSSREF]

2. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al.; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68. doi: 10.1164/rccm.201807-1255ST. [CROSSREF]

3. Fukihara J, Kondoh Y, Brown KK, Kimura T, Kataoka K, Matsuda T, et al. Probable usual interstitial pneumonia pattern on chest CT: is it sufficient for a diagnosis of idiopathic pulmonary fibrosis? Eur Respir J. 2020 Apr 9;55(4):1802465. doi: 10.1183/13993003.02465-2018. [CROSSREF]

4. Stjepanović M, Belić S, Buha I, Marić N, Baralić M, Mihailović-Vučinić V. Rapidly progressive pulmonary fibrosis in COVID-19 pneumonia. Srp Arh Celok Lek 2021. 149(7-8): 467–470.

5. Stankovic S, Stjepanovic M, Asanin M. Biomarkers in Idiopathic Pulmonary Fibrosis. Idiopathic Pulmonary Fibrosis. [Internet]. London: IntechOpen; 2021. [pristupljeno: novembar 2022.]. [HTTP]

6. Bennett D, Mazzei MA, Squitieri NC, Bargagli E, Refini RM, Fossi A, et al. Familial pulmonary fibrosis: Clinical and radiological characteristics and progression analysis in different high resolution-CT patterns. Respir Med. 2017 May;126:75-83. doi: 10.1016/j.rmed.2017.03.020. [CROSSREF]

7. Abramson MJ, Murambadoro T, Alif SM, Benke GP, Dharmage SC, Glaspole I; Australian IPF Registry. Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Australia: case-control study. Thorax. 2020 Oct;75(10):864-869. doi: 10.1136/thoraxjnl-2019-214478. [CROSSREF]

8. Frost A, Badesch D, Gibbs JSR, Gopalan D, Khanna D, Manes A, et al. Diagnosis of pulmonary hypertension. Eur Respir J. 2019 Jan 24;53(1):1801904. doi: 10.1183/13993003.01904-2018. [CROSSREF]

9. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237. [CROSSREF]

10. Nathan SD, Barbera JA, Gaine SP, Harari S, Martinez FJ, Olschewski H, et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J. 2019 Jan 24;53(1):1801914. doi: 10.1183/13993003.01914-2018. [CROSSREF]

11. Raghu G, Nathan SD, Behr J, Brown KK, Egan JJ, Kawut SM, et al. Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction. Eur Respir J. 2015 Nov;46(5):1370-7. doi: 10.1183/13993003.01537-2014. [CROSSREF]

12. Đurđević N, Belić S, Stjepanović M, Ašanin M. Plućna hipertenzija u hroničnoj opstruktivnoj bolesti pluća. Odabrana poglavlja u pulmologjji. Beograd. Medicinski fakultet u Beogradu, 2023.

13. Shorr AF, Wainright JL, Cors CS, Lettieri CJ, Nathan SD. Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant. Eur Respir J. 2007 Oct;30(4):715-21. doi: 10.1183/09031936.00107206. [CROSSREF]

14. Nathan SD, Shlobin OA, Ahmad S, Urbanek S, Barnett SD. Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. Chest. 2007 Mar;131(3):657-663. doi: 10.1378/chest.06-2485. [CROSSREF]

15. Mauban JR, Remillard CV, Yuan JX. Hypoxic pulmonary vasoconstriction: role of ion channels. J Appl Physiol (1985). 2005 Jan;98(1):415-20. doi: 10.1152/japplphysiol.00732.2004. [CROSSREF]

16. Huitema MP, Bakker ALM, Mager JJ, Rensing BJWM, Smits F, Snijder RJ, et al. Prevalence of pulmonary hypertension in pulmonary sarcoidosis: the first large European prospective study. Eur Respir J. 2019 Oct 31;54(4):1900897. doi: 10.1183/13993003.00897-2019. [CROSSREF]

17. Remy-Jardin M, Ryerson CJ, Schiebler ML, Leung ANC, Wild JM, Hoeper MM, et al. Imaging of Pulmonary Hypertension in Adults: A Position Paper from the Fleischner Society. Radiology. 2021 Mar;298(3):531-549. doi: 10.1148/ radiol.2020203108. [CROSSREF]

18. Ghio S, Mercurio V, Fortuni F, Forfia PR, Gall H, Ghofrani A; TAPSE in PAH investigators. A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension. Eur Respir J. 2020 Sep 24;56(3):2000513. doi: 10.1183/13993003.00513-2020. [CROSSREF]

19. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019 Jan 24;53(1):1801913. doi: 10.1183/13993003.01913-2018. [CROSSREF]

20. Hemnes AR, Opotowsky AR, Assad TR, Xu M, Doss LN, Farber-Eger E, et al. Features Associated With Discordance Between Pulmonary Arterial Wedge Pressure and Left Ventricular End Diastolic Pressure in Clinical Practice: Implications for Pulmonary Hypertension Classification. Chest. 2018 Nov;154(5):1099-1107. doi: 10.1016/j.chest.2018.08.1033. [CROSSREF]

21. Herve P, Lau EM, Sitbon O, Savale L, Montani D, Godinas L, et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J. 2015 Sep;46(3):728-37. doi: 10.1183/09031936.00021915. [CROSSREF]

22. Esfandiari S, Wolsk E, Granton D, Azevedo L, Valle FH, Gustafsson F, et al. Pulmonary Arterial Wedge Pressure at Rest and During Exercise in Healthy Adults: A Systematic Review and Meta-analysis. J Card Fail. 2019 Feb;25(2):114-122. doi: 10.1016/j.cardfail.2018.10.009. [CROSSREF]

23. Brownell R, Moua T, Henry TS, Elicker BM, White D, Vittinghoff E, et al. The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia. Thorax. 2017 May;72(5):424-429. doi: 10.1136/thoraxjnl-2016-209671. [CROSSREF]

24. Belić S, Đurđević N, Stjepanović M, Ašanin M. Terapija plućne arterijske hipertenzije. Odabrana poglavlja u pulmologjji. Beograd. Medicinski fakultet u Beogradu, 2023.

25. Galiè N, Channick RN, Frantz RP, Grünig E, Jing ZC, Moiseeva O, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019 Jan 24;53(1):1801889. doi: 10.1183/13993003.01889-2018. [CROSSREF]

26. Benza RL, Gomberg-Maitland M, Elliott CG, Farber HW, Foreman AJ, Frost AE, et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest. 2019 Aug;156(2):323-337. doi: 10.1016/j.chest.2019.02.004. [CROSSREF]

27. Hoeper MM, Kramer T, Pan Z, Eichstaedt CA, Spiesshoefer J, Benjamin N, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017 Aug 3;50(2):1700740. doi: 10.1183/13993003.00740-2017. [CROSSREF]

28. Hoeper MM, Pausch C, Olsson KM, Huscher D, Pittrow D, Grünig E, et al. COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur Respir J. 2022 Jul 7;60(1):2102311. doi: 10.1183/13993003.02311-2021. [CROSSREF]

29. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 Sep 30;351(14):1425-36. doi: 10.1056/NEJMra040291. [CROSSREF]

30. Shapiro S, Torres F, Feldman J, Keogh A, Allard M, Blair C, et al. Clinical and hemodynamic improvements after adding ambrisentan to background PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a suboptimal therapeutic response (ATHENA-1). Respir Med. 2017 May;126:84- 92. doi: 10.1016/j.rmed.2017.03.025. [CROSSREF]

31. Wardle AJ, Seager MJ, Wardle R, Tulloh RM, Gibbs JS. Guanylate cyclase stimulators for pulmonary hypertension. Cochrane Database Syst Rev. 2016 Aug 2;2016(8):CD011205. doi: 10.1002/14651858.CD011205.pub2. [CROSSREF]

32. Simonneau G, Channick RN, Delcroix M, Galiè N, Ghofrani HA, Jansa P, et al. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN. Eur Respir J. 2015 Dec;46(6):1711-20. doi: 10.1183/13993003.00364-2015. [CROSSREF]

33. Rubin LJ, Galiè N, Grimminger F, Grünig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. 2015 May;45(5):1303-13. doi: 10.1183/09031936.00090614. [CROSSREF]

34. Ghofrani HA, Grimminger F, Grünig E, Huang Y, Jansa P, Jing ZC, et al. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial. Lancet Respir Med. 2016 May;4(5):361-71. doi: 10.1016/S2213-2600(16)30019-4. [CROSSREF]

35. Poštić A, Stjepanović M, Marić N, Belić S, Dimić-Janjić S, Đurđević N, et al Značaj KL-6 u dijagnosticii i prognozi intersticijumskih bolesti pluća. Acta Clinica 2021; 2(1): 35-44.

36. Rajagopal K, Bryant AJ, Sahay S, Wareing N, Zhou Y, Pandit LM, et al. Idiopathic pulmonary fibrosis and pulmonary hypertension: Heracles meets the Hydra. Br J Pharmacol. 2021 Jan;178(1):172-186. doi: 10.1111/bph.15036. [CROSSREF]

1. Esposito DB, Lanes S, Donneyong M, Holick CN, Lasky JA, Lederer D, et al. Idiopathic Pulmonary Fibrosis in United States Automated Claims. Incidence, Prevalence, and Algorithm Validation. Am J Respir Crit Care Med. 2015 Nov 15;192(10):1200-7. doi: 10.1164/rccm.201504-0818OC. [CROSSREF]

2. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al.; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68. doi: 10.1164/rccm.201807-1255ST. [CROSSREF]

3. Fukihara J, Kondoh Y, Brown KK, Kimura T, Kataoka K, Matsuda T, et al. Probable usual interstitial pneumonia pattern on chest CT: is it sufficient for a diagnosis of idiopathic pulmonary fibrosis? Eur Respir J. 2020 Apr 9;55(4):1802465. doi: 10.1183/13993003.02465-2018. [CROSSREF]

4. Stjepanović M, Belić S, Buha I, Marić N, Baralić M, Mihailović-Vučinić V. Rapidly progressive pulmonary fibrosis in COVID-19 pneumonia. Srp Arh Celok Lek 2021. 149(7-8): 467–470.

5. Stankovic S, Stjepanovic M, Asanin M. Biomarkers in Idiopathic Pulmonary Fibrosis. Idiopathic Pulmonary Fibrosis. [Internet]. London: IntechOpen; 2021. [pristupljeno: novembar 2022.]. [HTTP]

6. Bennett D, Mazzei MA, Squitieri NC, Bargagli E, Refini RM, Fossi A, et al. Familial pulmonary fibrosis: Clinical and radiological characteristics and progression analysis in different high resolution-CT patterns. Respir Med. 2017 May;126:75-83. doi: 10.1016/j.rmed.2017.03.020. [CROSSREF]

7. Abramson MJ, Murambadoro T, Alif SM, Benke GP, Dharmage SC, Glaspole I; Australian IPF Registry. Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Australia: case-control study. Thorax. 2020 Oct;75(10):864-869. doi: 10.1136/thoraxjnl-2019-214478. [CROSSREF]

8. Frost A, Badesch D, Gibbs JSR, Gopalan D, Khanna D, Manes A, et al. Diagnosis of pulmonary hypertension. Eur Respir J. 2019 Jan 24;53(1):1801904. doi: 10.1183/13993003.01904-2018. [CROSSREF]

9. Humbert M, Kovacs G, Hoeper MM, Badagliacca R, Berger RMF, Brida M; ESC/ERS Scientific Document Group. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237. [CROSSREF]

10. Nathan SD, Barbera JA, Gaine SP, Harari S, Martinez FJ, Olschewski H, et al. Pulmonary hypertension in chronic lung disease and hypoxia. Eur Respir J. 2019 Jan 24;53(1):1801914. doi: 10.1183/13993003.01914-2018. [CROSSREF]

11. Raghu G, Nathan SD, Behr J, Brown KK, Egan JJ, Kawut SM, et al. Pulmonary hypertension in idiopathic pulmonary fibrosis with mild-to-moderate restriction. Eur Respir J. 2015 Nov;46(5):1370-7. doi: 10.1183/13993003.01537-2014. [CROSSREF]

12. Đurđević N, Belić S, Stjepanović M, Ašanin M. Plućna hipertenzija u hroničnoj opstruktivnoj bolesti pluća. Odabrana poglavlja u pulmologjji. Beograd. Medicinski fakultet u Beogradu, 2023.

13. Shorr AF, Wainright JL, Cors CS, Lettieri CJ, Nathan SD. Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant. Eur Respir J. 2007 Oct;30(4):715-21. doi: 10.1183/09031936.00107206. [CROSSREF]

14. Nathan SD, Shlobin OA, Ahmad S, Urbanek S, Barnett SD. Pulmonary hypertension and pulmonary function testing in idiopathic pulmonary fibrosis. Chest. 2007 Mar;131(3):657-663. doi: 10.1378/chest.06-2485. [CROSSREF]

15. Mauban JR, Remillard CV, Yuan JX. Hypoxic pulmonary vasoconstriction: role of ion channels. J Appl Physiol (1985). 2005 Jan;98(1):415-20. doi: 10.1152/japplphysiol.00732.2004. [CROSSREF]

16. Huitema MP, Bakker ALM, Mager JJ, Rensing BJWM, Smits F, Snijder RJ, et al. Prevalence of pulmonary hypertension in pulmonary sarcoidosis: the first large European prospective study. Eur Respir J. 2019 Oct 31;54(4):1900897. doi: 10.1183/13993003.00897-2019. [CROSSREF]

17. Remy-Jardin M, Ryerson CJ, Schiebler ML, Leung ANC, Wild JM, Hoeper MM, et al. Imaging of Pulmonary Hypertension in Adults: A Position Paper from the Fleischner Society. Radiology. 2021 Mar;298(3):531-549. doi: 10.1148/ radiol.2020203108. [CROSSREF]

18. Ghio S, Mercurio V, Fortuni F, Forfia PR, Gall H, Ghofrani A; TAPSE in PAH investigators. A comprehensive echocardiographic method for risk stratification in pulmonary arterial hypertension. Eur Respir J. 2020 Sep 24;56(3):2000513. doi: 10.1183/13993003.00513-2020. [CROSSREF]

19. Simonneau G, Montani D, Celermajer DS, Denton CP, Gatzoulis MA, Krowka M, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019 Jan 24;53(1):1801913. doi: 10.1183/13993003.01913-2018. [CROSSREF]

20. Hemnes AR, Opotowsky AR, Assad TR, Xu M, Doss LN, Farber-Eger E, et al. Features Associated With Discordance Between Pulmonary Arterial Wedge Pressure and Left Ventricular End Diastolic Pressure in Clinical Practice: Implications for Pulmonary Hypertension Classification. Chest. 2018 Nov;154(5):1099-1107. doi: 10.1016/j.chest.2018.08.1033. [CROSSREF]

21. Herve P, Lau EM, Sitbon O, Savale L, Montani D, Godinas L, et al. Criteria for diagnosis of exercise pulmonary hypertension. Eur Respir J. 2015 Sep;46(3):728-37. doi: 10.1183/09031936.00021915. [CROSSREF]

22. Esfandiari S, Wolsk E, Granton D, Azevedo L, Valle FH, Gustafsson F, et al. Pulmonary Arterial Wedge Pressure at Rest and During Exercise in Healthy Adults: A Systematic Review and Meta-analysis. J Card Fail. 2019 Feb;25(2):114-122. doi: 10.1016/j.cardfail.2018.10.009. [CROSSREF]

23. Brownell R, Moua T, Henry TS, Elicker BM, White D, Vittinghoff E, et al. The use of pretest probability increases the value of high-resolution CT in diagnosing usual interstitial pneumonia. Thorax. 2017 May;72(5):424-429. doi: 10.1136/thoraxjnl-2016-209671. [CROSSREF]

24. Belić S, Đurđević N, Stjepanović M, Ašanin M. Terapija plućne arterijske hipertenzije. Odabrana poglavlja u pulmologjji. Beograd. Medicinski fakultet u Beogradu, 2023.

25. Galiè N, Channick RN, Frantz RP, Grünig E, Jing ZC, Moiseeva O, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019 Jan 24;53(1):1801889. doi: 10.1183/13993003.01889-2018. [CROSSREF]

26. Benza RL, Gomberg-Maitland M, Elliott CG, Farber HW, Foreman AJ, Frost AE, et al. Predicting Survival in Patients With Pulmonary Arterial Hypertension: The REVEAL Risk Score Calculator 2.0 and Comparison With ESC/ERS-Based Risk Assessment Strategies. Chest. 2019 Aug;156(2):323-337. doi: 10.1016/j.chest.2019.02.004. [CROSSREF]

27. Hoeper MM, Kramer T, Pan Z, Eichstaedt CA, Spiesshoefer J, Benjamin N, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017 Aug 3;50(2):1700740. doi: 10.1183/13993003.00740-2017. [CROSSREF]

28. Hoeper MM, Pausch C, Olsson KM, Huscher D, Pittrow D, Grünig E, et al. COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension. Eur Respir J. 2022 Jul 7;60(1):2102311. doi: 10.1183/13993003.02311-2021. [CROSSREF]

29. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004 Sep 30;351(14):1425-36. doi: 10.1056/NEJMra040291. [CROSSREF]

30. Shapiro S, Torres F, Feldman J, Keogh A, Allard M, Blair C, et al. Clinical and hemodynamic improvements after adding ambrisentan to background PDE5i therapy in patients with pulmonary arterial hypertension exhibiting a suboptimal therapeutic response (ATHENA-1). Respir Med. 2017 May;126:84- 92. doi: 10.1016/j.rmed.2017.03.025. [CROSSREF]

31. Wardle AJ, Seager MJ, Wardle R, Tulloh RM, Gibbs JS. Guanylate cyclase stimulators for pulmonary hypertension. Cochrane Database Syst Rev. 2016 Aug 2;2016(8):CD011205. doi: 10.1002/14651858.CD011205.pub2. [CROSSREF]

32. Simonneau G, Channick RN, Delcroix M, Galiè N, Ghofrani HA, Jansa P, et al. Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN. Eur Respir J. 2015 Dec;46(6):1711-20. doi: 10.1183/13993003.00364-2015. [CROSSREF]

33. Rubin LJ, Galiè N, Grimminger F, Grünig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. 2015 May;45(5):1303-13. doi: 10.1183/09031936.00090614. [CROSSREF]

34. Ghofrani HA, Grimminger F, Grünig E, Huang Y, Jansa P, Jing ZC, et al. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial. Lancet Respir Med. 2016 May;4(5):361-71. doi: 10.1016/S2213-2600(16)30019-4. [CROSSREF]

35. Poštić A, Stjepanović M, Marić N, Belić S, Dimić-Janjić S, Đurđević N, et al Značaj KL-6 u dijagnosticii i prognozi intersticijumskih bolesti pluća. Acta Clinica 2021; 2(1): 35-44.

36. Rajagopal K, Bryant AJ, Sahay S, Wareing N, Zhou Y, Pandit LM, et al. Idiopathic pulmonary fibrosis and pulmonary hypertension: Heracles meets the Hydra. Br J Pharmacol. 2021 Jan;178(1):172-186. doi: 10.1111/bph.15036. [CROSSREF]


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