Hypertension In Chronic Lung Disease Research Articles

Pulmonary vascular disease in chronic lung diseases: cause or comorbidity?

To provide timely and relevant insights into the complex relationship between pulmonary vascular disease (PVD) and chronic lung disease (CLD), focusing on the causative and consequential dynamics between these conditions. There are shared pathogenic mechanisms between pulmonary arterial hypertension (PAH) and group 3 pulmonary hypertension, including altered expression of mediators and growth factors implicated in both conditions. Factors such as hypoxia, hypoxemia, and hypercapnia also contribute to pulmonary vascular remodelling and endothelial dysfunction. However, the role of hypoxia as the sole driver of pulmonary hypertension in CLD is being reconsidered, particularly in chronic obstructive pulmonary disease (COPD), with evidence suggesting a potential role for cigarette smoke products in initiating pulmonary vascular impairment. On the other hand, interstitial lung disease (ILD) encompasses a group of heterogeneous lung disorders characterized by inflammation and fibrosis of the interstitium, leading to impaired gas exchange and progressive respiratory decline, which could also play a role as a cause of pulmonary hypertension. Understanding the intricate interplay between the pulmonary vascular compartment and the parenchymal and airway compartments in respiratory disease is crucial for developing effective diagnostic and therapeutic strategies for patients with PVD and CLD, with implications for both clinical practice and research.

Impact of targeted pulmonary arterial hypertension therapies in severe pulmonary hypertension in chronic lung diseases.

Patients with severe pulmonary hypertension associated with chronic lung disease have a poor prognosis. Targeted pulmonary arterial hypertension therapies might improve exercise capacity and outcome, but there are no guidelines on treatments which are not recommended because of an unproven benefit, with discordant results from few studies in this context. The aim of our study was to evaluate targeted pulmonary arterial hypertension therapies for severe group 3 pulmonary hypertension patients. We conducted an observational retrospective monocentre study on patients with severe group 3 pulmonary hypertension diagnosed on right heart catheterisation treated with targeted therapies. Primary outcome was an improvement of the distance on 6-min walk test of ≥30 m. Secondary end-points included changes in haemodynamics (pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP)) and identification of potential predictive factors of therapeutic response. 139 patients were enrolled. Most patients had monotherapy with phosphodiesterase 5 inhibitors (n=128; 92%). Mean change in 6-min walk distance was +1.5 m after treatment (p=0.59). Forced expiratory volume in 1 s and forced vital capacity were not predictive factors for response. We found a significant improvement of PVR and mPAP of -1.0 Wood Units (p<0.001) and -4 mmHg (p<0.001), respectively, under treatment. 18% of patients had to withdraw treatment for intolerance. Treatment duration <3 months was associated with poor survival (hazard ratio 2.75, p=0.0005). Oral targeted pulmonary arterial hypertension therapies do not improve exercise capacity in patients with severe pulmonary hypertension associated with chronic lung disease, but could improve haemodynamic parameters.

Pulmonary Hypertension in Chronic Lung Diseases: What Role Do Radiologists Play?

Pulmonary hypertension (PH) is a pathophysiological disorder, defined by a mean pulmonary arterial pressure (mPAP) > 20 mmHg at rest, as assessed by right heart catheterization (RHC). PH is not a specific disease, as it may be observed in multiple clinical conditions and may complicate a variety of thoracic diseases. Conditions associated with the risk of developing PH are categorized into five different groups, according to similar clinical presentations, pathological findings, hemodynamic characteristics, and treatment strategy. Most chronic lung diseases that may be complicated by PH belong to group 3 (interstitial lung diseases, chronic obstructive pulmonary disease, combined pulmonary fibrosis, and emphysema) and are associated with the lowest overall survival among all groups. However, some of the chronic pulmonary diseases may develop PH with unclear/multifactorial mechanisms and are included in group 5 PH (sarcoidosis, pulmonary Langerhans' cell histiocytosis, and neurofibromatosis type 1). This paper focuses on PH associated with chronic lung diseases, in which radiological imaging-particularly computed tomography (CT)-plays a crucial role in diagnosis and classification. Radiologists should become familiar with the hemodynamical, physiological, and radiological aspects of PH and chronic lung diseases in patients at risk of developing PH, whose prognosis and treatment depend on the underlying disease.

Pulmonary hypertension in chronic lung diseases

Pulmonary hypertension in chronic lung diseases

Echocardiography Nomogram for Predicting Survival among Chronic Lung Disease Patients with Severe Pulmonary Hypertension.

Severe pulmonary hypertension in chronic lung diseases (severe CLD-PH) differs significantly from other types of PH in physiology and prognosis. We aimed to assess whether echocardiography helps predict long-term survival in patients with severe CLD-PH. This single-centre, observational cohort study enrolled 100 patients with severe CLD-PH (mean pulmonary arterial pressure ≥35 mm Hg or ≥25 mm Hg with cardiac index <2.0 L/min/m2 or pulmonary vascular resistance ≥6 Wood units) between 2009 and 2014. The population was randomly divided into a derivation and validation cohort in a 2:1 ratio. To construct a nomogram, a multivariable logistic regression model was applied, and scores were assigned based on the hazard ratio of independent echocardiographic predictors. Multivariate Cox hazards analysis identified the strongest predictors of mortality as pulmonary arterial systolic pressure (PASP), tricuspid annular plane systolic excursion, and right ventricular end-diastolic transverse dimension. The three independent predictors were entered into the nomogram. Compared with PASP alone, the nomogram resulted in an integrated discrimination improvement of 15.5% (95% confidence interval, 5.52–25.5%, p = 0.002) with a net improvement in model discrimination (C-statistic from 0.591 to 0.746). Using echocardiographic parameters, we established and validated a novel nomogram to predict all-cause death for patients with severe CLD-PH.

Clinical trials in group 3 pulmonary hypertension.

Despite worse outcomes associated with the development of pulmonary hypertension in chronic lung disease, there are no approved treatments for this population. The present review summarizes the recent clinical trials in World Symposium on Pulmonary Hypertension (WSPH) Group 3 pulmonary hypertension, with a particular focus on the study of pulmonary arterial hypertension (PAH)-targeted therapy. Multiple recent randomized controlled trials have studied a host of PAH-specific medications in the treatment of WSPH Group 3 pulmonary hypertension, including endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclins. In pulmonary hypertension associated with chronic obstructive lung disease (PH-COPD) and with interstitial lung disease (PH-ILD), most trials have shown conflicting or negative results, although they have been limited by variable patient populations and small sample sizes. Recent large-scale trial data demonstrate that inhaled treprostinil is associated with improved outcomes in the PH-ILD population. Although most PAH medications have not shown consistent benefit in the WSPH Group 3 population, recent work suggests that inhaled treprostinil has an important role in the treatment of PH-ILD. Efforts are ongoing to evaluate the efficacy of other medications, identify optimal treatment candidates, and define clinically meaningful endpoints in WSPH Group 3 pulmonary hypertension.

Pulmonary hypertension in chronic lung disease and hypoxia.

Pulmonary hypertension (PH) frequently complicates the course of patients with various forms of chronic lung disease (CLD). CLD-associated PH (CLD-PH) is invariably associated with reduced functional ability, impaired quality of life, greater oxygen requirements and an increased risk of mortality. The aetiology of CLD-PH is complex and multifactorial, with differences in the pathogenic sequelae between the diverse forms of CLD. Haemodynamic evaluation of PH severity should be contextualised within the extent of the underlying lung disease, which is best gauged through a combination of physiological and imaging assessment. Who, when, if and how to screen for PH will be addressed in this article, as will the current state of knowledge with regard to the role of treatment with pulmonary vasoactive agents. Although such therapy cannot be endorsed given the current state of findings, future studies in this area are strongly encouraged.

Pulmonary hypertension in chronic lung diseases: comparison to other pulmonary hypertension groups.

Group 3 pulmonary hypertension (PH) is a common complication of advanced chronic lung disease. Our hypothesis was that group 3 PH is associated with a more severe baseline presentation and a more severe prognosis compared to group 1 pulmonary arterial hypertension (PAH), chronic thromboembolic PH (group 4), and group 5 PH. We retrospectively analyzed consecutive incident PH patients in a single center between January 2006 and November 2014. Data were acquired from a prospective database. Clinical, functional, and hemodynamic characteristics, as well as survival, were compared between the four groups of precapillary PH. A total of 363 patients were analyzed; 164 patients (45.2%) belonged to group 1 PAH, 109 (30%) to group 3 PH, 65 (17.9%) to group 4 PH, and 25 (6.9%) to group 5 PH. Group 3 patients were predominantly male and were more frequently in New York Heart Association (NYHA) class III/IV. Patients with group 3 and 4 PH were older, had significantly lower 6-min walking distance (6MWD), higher mean pulmonary arterial pressure, higher pulmonary vascular resistance (PVR), and lower cardiac index (CI) than PAH patients. Group 3 and 5 patients had significantly lower total lung capacity (TLC), forced vital capacity (FVC), and FEV1; group 3 patients had the lowest carbon monoxide transfer coefficient values. PH therapy was used in 90.9% of group 3 patients. Univariate analysis of prognostic factors in the overall population showed that age, male gender, NYHA class, groups 3 and 4 PH (vs. PAH), 6MWD, FVC, TLC, carbon monoxide transfer coefficient (KCO), PVR, CI, and venous oxygen saturation were significantly associated with greater mortality. Multivariate analysis showed that age, PH group 4, 6MWD, and KCO but no longer PH group 3 were significantly associated with mortality. Patients with group 3 PH are older, have more severe baseline presentation and lower survival rates than PAH patients in univariate analysis, that seemed to be related to older age.

Pulmonary Hypertension in Chronic Lung Diseases

Pulmonary Hypertension in Chronic Lung Diseases

Pulmonary hypertension in chronic lung disease of infancy.

Advances in neonatal care have improved the survival of extremely preterm infants. Chronic lung disease (CLD) is a common complication of prematurity, seen in about a third of preterm babies. Further, pulmonary hypertension complicates the hospital course in about 18% of preterm infants, and the incidence is much higher in infants with established CLD. There is increasing interest in studying this population and understanding the underlying pathobiology behind the development of pulmonary hypertension, which could lead to better identification of at-risk patients as well as improved management strategies and therapeutic targets. Acknowledgement of this growing population of infants with pulmonary hypertension has led to modifications in the current WHO classification of pulmonary hypertension and the establishment of a subcategory for developmental lung disease with pulmonary hypertension. A number of recent publications have evaluated the use of targeted therapies in this population; however, there is a need for large controlled studies, to study the long-term efficacy and safety of these medications. This review will discuss the pathobiology of CLD with pulmonary hypertension and enumerate the current diagnostic and treatment modalities used by experts in the field. It will also suggest a diagnosis and management algorithm for infants suspected to have pulmonary hypertension in the newborn unit.

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension due to lung diseases and/or hypoxia.

Chronic lung diseases are common causes of pulmonary hypertension. It ranks second after the left heart disease. Both obstructive and restrictive lung diseases are know to cause pulmonary hypertension.The pathophysiology of the disease is complex, and includes factors affecting the blood vessels, airways, and lung parenchyma. Hypoxia and the inhalation of toxic materials are another contributing factors. Recent guidelines have further clarified the association between pulmonary hypertension and chronic lung disease and made general guidelines concerning the diagnosis and management.In this article, we will provide a detailed revision about the new classification and give general recommendations about the management of pulmonary hypertension in chronic lung diseases.

Circulation Research Thematic Synopsis

<i>Circulation Research</i> Thematic Synopsis

Pulmonary Artery Smooth Muscle Cell Senescence Is a Pathogenic Mechanism for Pulmonary Hypertension in Chronic Lung Disease

Senescence of pulmonary artery smooth muscle cells (PA-SMCs) caused by telomere shortening or oxidative stress may contribute to pulmonary hypertension associated with chronic lung diseases. To investigate whether cell senescence contributes to pulmonary vessel remodeling and pulmonary hypertension in chronic obstructive pulmonary disease (COPD). In 124 patients with COPD investigated by right heart catheterization, we found a negative correlation between leukocyte telomere length and pulmonary hypertension severity. In-depth investigations of lung vessels and derived cultured PA-SMCs showed greater severity of remodeling and increases in senescent p16-positive and p21-positive PA-SMCs and proliferating Ki67-stained cells in 14 patients with COPD compared to 13 age-matched and sex-matched control subjects who smoke. Cultured PA-SMCs from COPD patients displayed accelerated senescence, with fewer cell population doublings, an increased percentage of β-galactosidase-positive cells, shorter telomeres, and higher p16 protein levels at an early cell passage compared to PA-SMCs from controls. Both in situ and in vitro PA-SMC senescence criteria correlated closely with the degree of pulmonary vessel wall hypertrophy. Because senescent PA-SMCs stained for p16 and p21 were virtually confined to the media near the Ki67-positive cells, which predominated in the neointima and hypertrophied media, we evaluated whether senescent cells affected normal PA-SMC functions. We found that senescent PA-SMCs stimulated the growth and migration of normal target PA-SMCs through the production and release of paracrine soluble and insoluble factors. PA-SMC senescence is an important contributor to the process of pulmonary vascular remodeling that underlies pulmonary hypertension in chronic lung disease.

Plicní hypertenze u chronických plicních onemocnění

Plicni hypertenze u chronických plicnich onemocněni je definovana na rozdil od plicni arterialni hypertenze střednim tlakem v plicnici ≥ 20 mm Hg (u plicni arterialni hypertenze ≥ 25 mm Hg) a tlakem v zakliněni nižsim než 12 mm Hg. Prevalenci plicni hypertenze u plicnich onemocněni lze odhadnout na 2-6/1 000 nemocných, incidenci pak na 1-3/10 000 osob, což představuje 100krat castějsi incidenci než je incidence idiopaticke plicni arterialni hypertenze.Plicni hypertenze při chronicke obstrukcni plicni nemoci (CHOPN) je vyvolana alveolarni hypoventilaci, vedouci k alveolarni hypoxii a plicni vazokonstrikci. Jak akutni, tak chronicka hypoxie vyvolava plicni vazokonstrikci. Dochazi ke vzniku endotelialni dysfunkce a k remodelaci mensich plicnich arterii.Respiracni acidoza potencuje hypoxickou plicni hypertenzi a naopak respiracni alkaloza ji zeslabuje. Ke zhorseni plicni hypertenze při CHOPN přispiva i přitomnost polycytemie a hypervolemie u těžsich nemocných. Zakladem remodelace plicnich arterii je patrně poskozeni endotelu vyvolane hypoxii. Endotelialni dysfunkce vede ke zvýsene tvorbě vazokonstrikcnich latek - endotelinu a tromboxanu A2 a ke snižene tvorbě vazodilatacnich latek - NO a prostacyklinu.Remodelace plicnich cev při plicnich onemocněnich je charakterizovana hypertrofii svaloviny medie v drobných plicnich arteriich, vznikem svaloviny v plicnich arteriolach, proliferaci endotelialnich buněk i fibroblastů. Anatomicke změny plicnich arterii a arteriol jsou při plicnich onemocněnich reverzibilni.Existuje individualni variabilita ve vnimavosti plicnich cev vůci hypoxii u lidi. Tim lze castecně vysvětlit různe stupně plicni hypertenze u hypoxicke plicni hypertenze.Plicni hypertenze u CHOPN býva obvykle mirna až středně těžka. Středni tlak v plicnici se pohybuje mezi 20-42 mm Hg. Progrese plicni hypertenze je pomala. Plicni hypertenze progreduje průměrně o 0,5-0,6 mm Hg za rok. Rychlejsi progresi vykazuji pacienti s těžkou hypoxemii nebo pacienti s těžkou plicni hypertenzi.Nejdřive je středni tlak v plicnici normalni v klidu, ale při zatěži 40 W v rovnovažnem stavu stoupa středni tlak v plicnici nad 30 mm Hg - hovořime o plicni hypertenzi při zatěži.Přitomnost plicni hypertenze při zatěži znaci větsi pravděpodobnost vzniku pozdějsi klidove plicni hypertenze. Opětovane vzestupy tlaku v plicnici při zatěži přispivaji patrně ke vzniku srdecniho selhani. Rovněž během spanku (zejmena REM spanku) se zhorsuje plicni hypertenze paralelně se zhorsenim hypoxemie.Ke zhorseni plicni hypertenze dochazi během akutnich infekci dýchacich cest paralelně se zhorsenim respirace, kdy středni tlak v plicnici stoupa i o 20 mm Hg a tyto epizody mohou přispět ke vzniku pravostranneho srdecniho selhani.Těžka plicni hypertenze se vyskytuje jen asi u 10 % pacientů s CHOPN s výjimkou situaci, kdy jsou tito vysetřeni během akutni exacerbace, nebo pokud jsou obezni s alveolarnim hypoventilacnim syndromem nebo syndromem spankove apnoe. Těžkou plicni hypertenzi mohou způsobit dalsi onemocněni, jako onemocněni leveho srdce (mitralni nebo aortalni vady), levostranne srdecni selhani, ICHS, hypertenze, kardiomyopatie a plicni embolizace. Mezi přiciny těžke plicni hypertenze u CHOPN patři individualni rozdily v reaktivitě plicnich cev na hypoxii, rozdily v intenzitě remodelace i geneticke rozdily. Cevni přestavba u těchto pacientů připomina přestavbu plicnich cev u plicni arterialni hypertenze.Přestože plicni hypertenze býva u plicnich onemocněni větsinou mirna, meně casto středně těžka a zřidka těžka, je středni tlak v plicnici i v multivariacni analýze nejlepsim prediktorem životni prognozy.Pokrok v neinvazivni diagnostice plicni hypertenze přinesla dopplerovska echokardiografie. U pacientů s CHOPN vsak skýta někdy nemale obtiže. Důležite je odhaleni dilatace prave komory. Pro posouzeni přitomnosti hypertrofie prave komory je významne stanoveni tlousťky volne stěny prave komory. Chyběni abnormalit velikosti a funkce prave komory větsinou vylucuje plicni hypertenzi.Nejdřive je ejekcni frakce prave komory normalni v klidu a při zatěži se dale zvysuje. Při dalsi progresi je ejekcni frakce prave komory v klidu sice normalni, ale při zatěži nestoupa, později dokonce paradoxně klesa. Při klidove plicni hypertenzi býva ejekcni frakce prave komory již v klidu snižena. Posouzeni funkce prave komory v klidu a při zatěži je možne radionuklidovou ventrikulografii a echokardiografii. Posouzeni funkce a velikosti prave komory lze provest take spiralni CT-angiografii nebo nejlepe NMR.Zavěr přehledu upozorňuje na obtiže v diagnostice pravostranneho srdecniho selhani a vymezuje možnou ulohu vazodilatacni lecby předevsim u pacientů s těžkou plicni hypertenzi.

Brain Natriuretic Peptide Is a Prognostic Parameter in Chronic Lung Disease

The detection of pulmonary hypertension in patients with chronic lung disease has prognostic implications. The brain natriuretic peptide (BNP) has been suggested as a noninvasive marker for the presence and severity of pulmonary hypertension. We evaluated circulating BNP levels as a parameter for the presence and severity of pulmonary hypertension in patients with chronic lung disease. BNP levels were measured in 176 consecutive patients with various pulmonary diseases. Right heart catheterization, lung functional testing, and a 6-min walk test were performed. The mean follow-up time was nearly 1 yr. Significant pulmonary hypertension (mean pulmonary artery pressure > 35 mm Hg) was diagnosed in more than one-fourth of patients and led to decreased exercise tolerance and life expectancy. Elevated BNP concentrations identified significant pulmonary hypertension with a sensitivity of 0.85 and specificity of 0.88 and predicted mortality. Moreover, BNP served as a risk factor of death independent of lung functional impairment or hypoxemia in uni- and multivariate analysis. We suggest BNP as a prognostic marker and as screening parameter for significant pulmonary hypertension in chronic lung disease.

Recent advances in diagnosis and management of pulmonary hypertension in chronic lung disease.

Pulmonary hypertension with elevated pulmonary vascular resistance is a common cardiovascular complication associated with increased morbidity and mortality in preterm infants with chronic lung disease. Injury to the developing pulmonary circulation results in structural and functional abnormalities of the pulmonary vasculature. Animal studies have demonstrated that disruption of angiogenesis may contribute to the failure of normal alveolarisation in chronic lung disease. Levels of vascular endothelial growth factor in bronchoalveolar lavage fluid are lower in infants with chronic lung disease compared to preterm controls. Supplemental oxygen is commonly used to prevent and treat pulmonary hypertension, although optimal arterial oxygen saturation levels remain uncertain. Other vasodilators such as inhaled nitric oxide appear promising, but as yet have not been evaluated in the form of randomised controlled trials. Further studies are required to investigate the long-term effectiveness of pulmonary vasodilator therapy.

Recent advances in diagnosis and management of pulmonary hypertension in chronic lung disease

Recent advances in diagnosis and management of pulmonary hypertension in chronic lung disease

Structural basis of hypoxic pulmonary hypertension: the modifying effect of chronic hypercapnia.

Exposure to chronic hypoxia causes pulmonary hypertension and pulmonary vascular remodelling. In chronic lung disease, chronic hypercapnia frequently coexists with hypoxia and is associated with worsening of pulmonary hypertension. It is generally stated that pulmonary hypertension in these conditions is secondary to hypoxic vascular remodelling and that hypercapnia augments this remodelling thus worsening the hypertension. We review recent evidence which shows that although chronic hypoxia causes thickening of the walls of pulmonary arterioles, these changes do not lead to structural narrowing of the lumen by encroachment. Moreover, hypoxia leads to new vessel formation within the pulmonary vasculature and not loss of vessels as formerly thought. Such neovascularization may provide a beneficial adaptation by increasing the area of the gas exchange membrane. These novel structural findings are supported by recent reports that inhibitors of the RhoA pathway can acutely reduce pulmonary vascular resistance in chronically hypoxic lungs to near normal values, demonstrating that structural changes are not the dominant mechanisms underling hypoxic pulmonary hypertension. Chronic hypercapnia inhibits the development of hypoxic pulmonary hypertension, pulmonary vascular remodelling and hypoxia-induced angiogenesis. This last effect might be maladaptive, as it would prevent the potentially beneficial increase in gas exchange membrane area. These findings suggest that structural narrowing of the vascular lumen of resistance vessels is not the mechanism by which hypoxia and hypercapnia cause pulmonary hypertension in chronic lung disease.

Symposium on the respiratory system

The summer 2001 meeting of the Anatomical Society of Great Britain and Ireland was held at University College, Dublin, on 10–12 July, and included a symposium on the biology of the respiratory system. It was the intention of the organizers to assemble a panel of speakers who could give the broadest possible view on this subject. The respiratory system is well suited to such a broad perspective since it has interdependencies with so many other systems as well as a rich phylogenetic and ontogenetic history. This symposium issue of the Journal of Anatomy presents the material covered by each speaker at the meeting. J. N. Maina shows how the comparative morphology of gas exchange mechanisms demonstrates the enormous range of strategies evolved by various taxa to deal with the problems of respiratory exchange under different environmental conditions. In addition to the tissues directly involved in gas exchange, adaptations were also needed in ancillary structures such as the diaphragm, body wall and the musculoskeletal anatomy of the air-conduction passages. M. Pickering and J. F. X. Jones consider how the dual evolutionary origin of the diaphragm is reflected by its current functional anatomy. J. H. Widdicombe gives insights into the complex mechanisms of ciliary action and mucous secretion, an essential requirement for protection of the respiratory epithelia from harmful elements in the external environment of air-breathing vertebrates. Efficient respiration also requires adaptations elsewhere, such as the central nervous and cardiovascular systems, to ensure that the respiratory movements are matched to the metabolic needs of the organism. J. F. R. Paton and M. Dutschmann describe the importance of central control of the glottis for functionally healthy breathing; A. Hislop gives a fascinating account of how the ontogenetic development of the respiratory organs and tissues involves a harmonious interdependence between the development and growth of the respiratory epithelia and that of the vasculature. Demands for adaptation are also made on the mature respiratory system in disease states. As N. Hopkins and P. McLoughlin show, the occurrence of pulmonary hypertension in chronic lung disease raises interesting questions. For example, why does the pulmonary vasculature have a different response to chronic hypoxia compared to the systemic? Is it possible that angiogenesis may occur in the chronically diseased adult lung as a means of modifying hypertension? Is it possible that vascular and other adaptations to disease in the mature lung may be achieved via pathways that are the same as those in normal lung development? We can expect to see efforts to investigate these issues intensifying in the coming years.

The structural basis of pulmonary hypertension in chronic lung disease: remodelling, rarefaction or angiogenesis?

Chronic lung disease in humans is frequently complicated by the development of secondary pulmonary hypertension, which is associated with increased morbidity and mortality. Hypoxia, inflammation and increased shear stress are the primary stimuli although the exact pathways through which these initiating events lead to pulmonary hypertension remain to be completely elucidated. The increase in pulmonary vascular resistance is attributed, in part, to remodelling of the walls of resistance vessels. This consists of intimal, medial and adventitial hypertrophy, which can lead to encroachment into and reduction of the vascular lumen. In addition, it has been reported that there is a reduction in the number of blood vessels in the hypertensive lung, which could also contribute to increased vascular resistance. The pulmonary endothelium plays a key role in mediating and modulating these changes. These structural alterations in the pulmonary vasculature contrast sharply with the responses of the systemic vasculature to the same stimuli. In systemic organs, both hypoxia and inflammation cause angiogenesis. Furthermore, remodelling of the walls of resistance vessels is not observed in these conditions. Thus it has been generally stated that, in the adult pulmonary circulation, angiogenesis does not occur. Prompted by previous observations that chronic airway inflammation can lead to pulmonary vascular remodelling without hypertension, we have recently shown, using quantitative stereological techniques, that angiogenesis can occur in the adult pulmonary circulation. Pulmonary angiogenesis has also been reported in some other conditions including post-pneumonectomy lung growth, metastatic disease of the lung and in biliary cirrhosis. Such angiogenesis may serve to prevent or attenuate increased vascular resistance in lung disease. In view of these more recent data, the role of structural alterations in the pulmonary vasculature in the development of pulmonary hypertension should be carefully reconsidered.