Phenotypes of Sarcoidosis-Associated Pulmonary Hypertension-A Challenging Mystery.

Sarcoidosis has been a well-recognised risk factor for pulmonary hypertension (PH) for a long time, but still, the knowledge about this concatenation is incomplete. Sarcoidosis-associated PH (SAPH) is an uncommon but serious complication associated with increased morbidity and mortality among sarcoidosis patients. The real epidemiology of SAPH remains unknown, and its pathomechanisms are not fully explained. Sarcoidosis is a heterogeneous and dynamic condition, and SAPH pathogenesis is believed to be multifactorial. The main roles in SAPH development play: parenchymal lung disease with the destruction of pulmonary vessels, the extrinsic compression of pulmonary vessels by conglomerate masses, lymphadenopathy or fibrosing mediastinitis, pulmonary vasculopathy, LV dysfunction, and portal hypertension. Recently, it has been recommended to individually tailor SAPH management according to the predominant pathomechanism, i.e., SAPH phenotype. Unfortunately, SAPH phenotyping is not a straightforward process. First, there are gaps in our understanding of undergoing processes. Second, the assessment of such a pivotal element as pulmonary vasculature on a microscopic level is non-feasible in SAPH patients antemortem. Finally, SAPH is a dynamic condition, multiple phenotypes usually coexist, and patients can switch between phenotypes during the course of sarcoidosis. In this article, we summarise the basic knowledge of SAPH, describe SAPH phenotypes, and highlight some practical problems related to SAPH phenotyping.

Pulmonary Hypertension in the Course of Interstitial Lung Diseases-A Personalised Approach Is Needed to Identify a Dominant Cause and Provide an Effective Therapy.

The prevalence of pulmonary hypertension (PH) complicating interstitial lung diseases (ILDs) is 3.5-15% at an early stage, and up to 90% in ILD patients listed for lung transplantation. In addition, other types of PH may occur in patients with ILDs due to concomitant conditions. Therefore, any significant PH occurring in the setting of ILD requires a proper differential workup. PH increases morbidity and mortality in ILDs. The pathomechanisms underlying PH due to ILD (PH-ILD) are not fully known, and there is no straightforward correlation between the presence or severity of PH-ILD and the severity of ILD. Severe PH in mild ILD without other explanatory causes constitutes a dilemma of differentiating between PH due to ILD and pulmonary arterial hypertension coexisting with ILDs. The heterogeneity and poor prognosis of patients with ILDs coexisting with PH necessitate an individualised approach to the management of this condition. This review presents recent advances in understanding and treatment options in PH-ILD. It also addresses practical issues, such as when to suspect and how to screen for PH in ILD, what are the indications for right heart catheterisation, and how to approach an individual ILD patient to determine the dominant PH cause and apply adequate management.

Atypical Pulmonary Tuberculosis as the First Manifestation of Advanced HIV Disease-Diagnostic Difficulties.

Tuberculosis (TB) is the leading cause of morbidity, hospitalisations, and mortality in people living with HIV (PLWH). The lower CD4+ T-lymphocyte count in the course of HIV infection, the higher risk of active TB, and the higher odds for atypical clinical and radiologic TB presentation. These HIV-related alterations in TB presentation may cause diagnostic problems in patients not knowing they are infected with HIV. We report on a patient without any background medical conditions, who was referred to a hospital with a 4-month history of chest and feet pains, mild dry cough, fatigue, reduced appetite, and decreasing body weight. Chest X-ray revealed mediastinal lymphadenopathy, bilateral reticulonodular parenchymal opacities, and pleural effusion. A preliminary diagnosis of lymphoma, possibly with a superimposed infection was established. Further differential diagnostic process revealed pulmonary TB in the course of advanced HIV-1 disease, with a CD4+ T-lymphocyte count of 107 cells/mm3. The patient completed anti-tuberculous therapy and successfully continues on antiretroviral treatment. This case underlines the importance of screening for HIV in patients with newly diagnosed TB.

Predictive value of chest HRCT for survival in idiopathic pulmonary arterial hypertension.

BACKGROUND: Little attention has been paid to chest high resolution computed tomography (HRCT) findings in idiopathic pulmonary arterial hypertension (IPAH) patients so far, while a couple of small studies suggested that presence of centrilobular ground-glass opacifications (GGO) on lung scans could have a significant negative prognostic value. Therefore, the aims of the present study were: to assess frequency and clinical significance of GGO in IPAH, and to verify if it carries an add-on prognostic value in reference to multidimensional risk assessment tool recommended by the 2015 European pulmonary hypertension guidelines. METHODS: Chest HRCT scans of 110 IPAH patients were retrospectively analysed. Patients were divided into three groups: with panlobular (p)GGO, centrilobular (c)GGO, and normal lung pattern. Association of different GGO patterns with demographic, functional, haemodynamic, and biochemical parameters was tested. Survival analysis was also performed. RESULTS: GGO were found in 46% of the IPAH patients: pGGO in 24% and cGGO in 22%. Independent predictors of pGGO were: positive history of haemoptysis, higher number of low-risk factors, and lower cardiac output. Independent predictors of cGGO were: positive history of haemoptysis, younger age, higher right atrial pressure, and higher mixed venous blood oxygen saturation. CGGO had a negative prognostic value for outcome in a 2-year perspective. This effect was not seen in the longer term, probably due to short survival of cGGO patients. CONCLUSIONS: Lung HRCT carries a significant independent prognostic information in IPAH, and in patients with cGGO present on the scans an early referral to lung transplantation centres should be considered.

Pulmonary actinomycosis complicated by fistula of the chest wall.

Actinomycosis is a rare disease caused by Actinomyces spp. The clinical and radiological picture of the disease is uncharacter-istic, which delays the diagnosis and can lead to complications. We present a case of pulmonary actinomycosis complicated by a chest wall fistula in a 43-year-old man with advanced tooth decay. The patient was admitted to our Department due to a chest wall fistula with bloody discharge. A few months earlier, he was treated with antibiotics for pneumonia. Since then, weakness, exertional dyspnoea, and weight loss had been observed. On admission, increased inflammatory markers were found in laboratory tests. Chest computed tomography (CT) revealed right-sided encapsulated pleural fluid collection containing gas bubbles, pleural thickening, anterior thoracic wall soft tissues thickening and subcutaneous fat stranding. CT suggested an empyema or a breast either pleural malignancy. The picture suggested a breast or pleural tumour to differentiate with an empyema. Videothoracoscopy was performed, the histological examination of the collected samples revealed granulation tissue and bacterial colony of a morphology corresponding to Actinomyces spp. Pulmonary actinomycosis was diagnosed. Antibiotic therapy according to the guidelines was initiated and dental treatment was recommended. Healing of the fistula and significant regression of lesions in the right lung were achieved. Although it is a rare disease, actinomycosis should be considered in the differential diagnosis of any chronic infiltrative lung lesions.

Pulmonary veno-occlusive disease: pathogenesis, risk factors, clinical features and diagnostic algorithm - state of the art.

Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary haemangiomatosis (PCH) are rare disorders, with the estimated prevalence of less than 1 case per million inhabitants. The vascular pathology in PVOD/PCH involves pre-septal and septal veins, alveolar capillaries and small pulmonary arteries. According to the ERS/ESC classification of pulmonary hypertension (PH) from 2015, PVOD/PCH have been included in the subgroup 1' of pulmonary arterial hypertension (PAH). Recent data indicate, however, the possibility of PVOD/PCH pathology in the patients diagnosed in the group 1. The problem may concern PAH associated with scleroderma, drug- induced PAH, PAH due to HIV infection and up to 10% of patients with idiopathic PAH (IPAH). Recently, bi-allelic EIF2AK4 mutations were found in the cases with heritable form of PVOD/PCH and in about 9% of sporadic cases. Moreover, an association between occupational exposure to organic solvents and PVOD/PCH was proved. The present review is an attempt to summarise the current data on pathogenesis, risk factors, clinical features and diagnostic algorithm for PVOD/PCH.

Sarcoidosis-associated pulmonary hypertension treated with sildenafil - a case report.

Development of sarcoidosis-associated pulmonary hypertension (SAPH) significantly worsens prognosis in sarcoidosis patients. Unfortunately, there is no treatment of proven benefit for this condition. Medications used for treatment of pulmonary arterial hypertension are of great interest in this respect. Here, we report a case of a patient with severe SAPH treated with sildenafil. A significant, but only temporary improvement in functional status was observed, and the patient died of gradually progressing heart and respiratory failure while awaiting for lung transplantation.

Pulmonary hypertension in diffuse parenchymal lung diseases - is there any benefit of PAH-specific therapy?

Pulmonary hypertension (PH) is diagnosed in 40-50% of the patients with end-stage diffuse parenchymal lung diseases (DPLD), and it is associated with significant worsening of life expectancy. Latest ERS/ESC guidelines recommend best available treatment of DPLD, and long-term oxygen therapy in the patients with PaO2 less than 60 mm Hg. Pulmonary arterial hypertension (PAH)-targeted drugs are not recommended in PH-DPLD patients, due to the risk of increasing the ventilation-perfusion mismatch, and consequently worsening of hypoxaemia. Nevertheless, PAH-oriented treatment may be beneficial to selected groups of patients. The authors try to find the answer to several important questions: is there any benefit of PAH-specific therapy in PH-DPLD, who should be the candidate for PAH-specific therapy, what class of drugs is most promising, and what outcome measures should be employed?

Respiratory system involvement in inflammatory bowel diseases.

Inflammatory bowel diseases are systemic disorders that can manifest in any location. The problem of respiratory system involvement is very important form clinical point of view. In the article we try to systematize the current knowledge on this topic.

Centrilobular nodules in high resolution computed tomography of the lung in IPAH patients - preliminary data concerning clinico-radiological correlates.

INTRODUCTION: Inhomogeneity of lung attenuation pattern is observed in high resolution chest computed tomography (HRCT) in some IPAH patients despite lack of interstitial lung disease. Such radiological changes are described either as ill-defined centrilobular nodules (CN) or as focal ground glass opacities (FGGO). There is no consensus in the literature, whether they indicate the distinct type of IPAH, or pulmonary venoocclusive disease (PVOD) with subtle radiological changes. Thus the aim of the present pilot study was to assess the frequency and clinical significance of inhomogenic lung attenuation pattern in IPAH. MATERIAL AND METHODS: 52 IPAH patients (38 females, 14 males, mean age 41 years ± 15 years), entered the study. All available chest CT scans were reviewed retrospectively by the experienced radiologist, not aware about the clinical data of the patients. RESULTS: CN were found in 10 patients (19%), FGGO - in 12 patients (23%). No lymphadenopathy or interlobular septal thickening suggestive of PVOD were found. The significant differences between CN and the remaining patients included: lower mean age - 31 and 43.5 years, (p = 0.02), lack of persistent foramen ovale (PFO) - 0% and 43% (p = 0.03), and higher mean right atrial pressure (mRAP) - 12.5 mm Hg and 7.94 mm Hg (p = 0.01). No significant survival differences were observed between the groups of CN, FGGO and the remaining patients. CONCLUSION: Centrilobular nodules in IPAH were combined with lack of PFO, higher mRAP and younger age of patients.

Low DLCO in idiopathic pulmonary arterial hypertension - clinical correlates and prognostic significance.

INTRODUCTION: Decreased diffusing capacity of the lung for carbon monoxide (DLCO) is observed in some idiopathic pulmonary arterial hypertension (IPAH) patients, but its clinical significance is uncertain. We aimed to assess clinical correlates and prognostic significance of low DLCO in IPAH patients. MATERIAL AND METHODS: In the group of 65 IPAH patients the cut off value for low DLCO was set up based on histogram as < 55% of predicted value. Demographic data, exercise capacity, lung function tests, hemodynamic parameters and survival of the patients were compared depending on DLCO value. RESULTS: Low DLCO was found in 18% of the patients, and it was associated with male sex, older age, worse functional status and exercise capacity, and higher prevalence of coronary artery disease. Low DLCO carried a 4-fold increase of death risk in 5-year perspective. CONCLUSIONS: Low DLCO was a marker of worse functional capacity and increased risk of death in studied IPAH patients.

Non-high risk PE in the patients with acute or exacerbated respiratory disease: the value of the algorithm based on D-dimer evaluation and Revised Geneva Score.

INTRODUCTION: The diagnostic algorithm of non-high risk pulmonary embolism (PE) is based on probability scoring systems and plasma D-dimer (DD) assessment. The aim of the present study was to investigate the efficacy of Revised Geneva Scoring (RGS) and DD testing for the excluding of non-high risk PE, in the patients admitted to the hospital due to acute respiratory diseases. MATERIAL AND METHODS: The consecutive patients, above 18 years of age, referred to the department of lung diseases, entered the study. The exclusion criteria were: the pregnancy and the suspicion of high risk PE. Plasma DD was measured with quick ELISA test, VIDAS D-dimer New, bioMerieux, France. Multislice computed tomography angiography was performed in all of the patients. RESULTS: 153 patients, median age 65 (19-88) years entered the study. The probability of PE was: low - in 58 patients (38%), intermediate - in 90 (59%), high - in 5 (3%). DD < 500 ng/ml was found in 12% of patients with low and intermediate probability of PE. PE was recognized in 10 out of 153 patients (7%). None of the patients with DD < 500 ng/ml was diagnosed with PE (NPV 100%). Median DD value was significantly higher in PE patients comparing to non-PE (4500 ng/ml and 1356 ng/ml respectively, p = 0.006). CONCLUSION: In the group of the patients with acute respiratory symptoms, low or intermediate clinical probability scoring combined with normal DD had a high NPV in excluding PE. Nevertheless, such approach was not very effective, as the increased DD was noted in 88% of the examined population.

Pulmonary hypertension in the course of diffuse parenchymal lung diseases - state of art and future considerations.

Lung diseases are one of the most frequent causes of pulmonary hypertension (PH). The development of PH influences the course of lung disease, worsening the clinical symptoms and prognosis. According to the most recent publications, PH in the course of lung diseases develops as a result of both "parenchymal" and vascular pathology, in the patients with genetic predisposition. Prolonged infection (especially viral one) may be an additional promoting factor. Right heart catheterization (RHC), which is an invasive procedure, is the only objective method of diagnosing PH. According to the latest recommendations, the management algorithm of PH and coexisting interstitial lung disease is based on RHC and the results of pulmonary function tests. Majority of the patients develop mild PH in the course of advanced lung disease. Best treatment of underlying lung pathology combined with long term oxygen treatment is recommended in this group. In case of severe PH (mean resting pulmonary artery pressure (mPAP) ≥ 35 mm Hg) the alternate cause of PH has to be sought. PAH-specific drugs use should be limited to patients with severe PH participating in clinical trials. In this review, the value of various non-invasive methods (echocardiography, radiological examination, exercise capacity and brain natriuretic peptides assessment) in the process of screening for PH is presented, and the results of recent randomized clinical trials with PAH-specific drugs in patients with diffuse parenchymal lung diseases are discussed.

Prognostic value of serum C-reactive protein (CRP) and cytokeratin 19 fragments (Cyfra 21-1) but not carcinoembryonic antigen (CEA) in surgically treated patients with non-small cell lung cancer.

INTRODUCTION: The aim of the study was to assess the prognostic value of cytokeratin 19 fragments (Cyfra 21-1), carcinoembryonic antigen (CEA) and C-reactive protein (CRP) in surgically treated NSCLC patients. MATERIAL AND METHODS: 50 NSCLC patients (25 adenocarcinoma, 21 squamous cell and 4 adenosquamous), clinical stages I and II, age 42-89 years, entered the study. CEA, Cyfra 21-1 and CRP concentrations were measured in serum taken before surgery, CEA and Cyfra 21-1 in 50 patients, CRP - in 46 patients. The survival was calculated from the date of surgical treatment until death or until the end of the observation time. The results were expressed as medians (95%CI). RESULTS: Cyfra 21-1 concentration was 2.1 (0.7-14.5) ng/mL. Survival time in the patients with Cyfra 21-1 ≤ 2 ng/mL, and > 2 ng/ /mL was 79 (14.85-88.2) and 29 (5.7-87.6) months, (p < 0.026). CEA concentration was 2.68 (0.87-72.7) ng/mL, significantly higher in adenocarcinoma than in squamous cell lung cancer - 4.38 ng/mL (1.67-41.35) vs. 2.2 ng/mL (1.0-6.1), p = 0.002. CRP concentration was 5.45 (0-122.6) mg/L. Significant dependence was found between CRP and pathological tumour size (pT). Median CRP values in pT1, pT2 and pT3+4 tumours were: 2.8 mg/L, 6.9 mg/L and 23.5 mg/L, respectively. Survival time of the patients with CRP ≤ 10 mg/L and CRP > 10 mg/L was 79 (14.85-88.2) and 29.5 (5.7-87.6) months, respectively (p = 0.045). CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only significant preoperative prognostic indicators (HR 2.08 and 2.04, respectively). Among the postoperative parameters, pathological stage of disease (p-stage) and pT were the significant prognostic indicators (HR 2.1 and 2.42, respectively). CONCLUSIONS: In the present study, concerning surgically treated NSCLC patients, preoperative CRP > 10 mg/L and Cyfra 21-1 > 2 ng/mL were the only negative prognostic indicators, while pT and p-stage were significant postoperative prognostic indicators.

Pulmonary pathology in patients with ulcerative colitis treated with mesalazine--a challenging and complex diagnostic problem. Case series and literature review.

Pulmonary involvement in the course of inflammatory bowel disease has been a subject of interest to clinicians for long time, but despite this, its epidemiology and potential pathomechanisms remain obscured. Equally unclear is the role of medications used for bowel disease treatment in lung disease development. We present three patients with ulcerative colitis, all treated with mesalazine, in whom unexplained lung disease developed. Due to different clinical and radiological presentation, different conditions were initially placed on the top of the differential list in each of them. The outcome was favourable in all patients despite differences in management. We compared our patients with similar cases from literature. We show the level of difficulty and complexity in the issue of lung disease in patients with inflammatory bowel disease.

In search of markers of treatment failure and poor prognosis in IPAH - the value of mosaic lung attenuation pattern on thin-section CT scans.

Despite the development of specific therapies for pulmonary arterial hypertension (PAH) some patients fail to respond to such treatment. One of the potential reasons for the unresponsiveness to targeted therapies may be the presence of fibrous occlusion of small pulmonary veins that accompanies pre-capillary arteriopathy. This type of pathologic change is called pulmonary veno-occlusive disease (PVOD). Underdiagnosed PVOD occurs probably in 5-10% of idiopathic pulmonary hypertension (IPAH) and in a substantial proportion of PAH related to connective tissue diseases (mainly in scleroderma). A definite diagnosis of PVOD requires histological examination of lung sample, but surgical lung biopsy in pulmonary hypertension is combined with high risk of bleeding. Thus major interest is focused on a non-invasive diagnostic approach enabling early recognition of PVOD and referral for lung transplantation. The present review is focused on the radiological features suggestive of PVOD-like vasculopathy in PAH.

[Abnormalities in high-resolution computed tomography of the lungs in patients with idiopathic pulmonary arterial hypertension -- correlation with hemodynamic parameters and prognostic significance]. / [Zmiany w tomografii komputerowej pluc o wysokiej rozdzielczosci u chroych na idiopatyczne tetnicze nadcisnienie plucne--powiazanie z parametrami hemodynamicznymi i znaczenie rokownicze.

INTRODUCTION: The risk stratification in idiopathic pulmonary arterial hypertension (IPAH) patients is currently based on haemodynamic and functional parameters as well as serum biomarker concentrations. Until now the importance of changes appearing in high-resolution computed tomography (HRCT) of the lungs of patients with IPAH has not been investigated. MATERIAL AND METHODS: Lung HRCT scans were analysed retrospectively in 48 IPAH patients (patients): 37 women, 11 men, mean age 41 +/- 15 years. RESULTS: Focal ground-glass opacifications (FGG) were found in 12 patients (25%), and centrilobular nodules (CN) were found in 8 patients (17%). In the remaining 58% of patients HRCT revealed no changes (N). Significantly lower stroke volume was found in the CN group (41.0 +/- 8.5 ml) compared to 60.8 +/- 15.1 ml in the FGG group and 58.1 +/- 18.0 ml in the N group (p = 0.03). Right atrial pressure was significantly higher in the CN group (12.2 +/- 4.86 mm Hg) than in the FGG group (6.9 +/- 3.9 mm Hg) and the N group (7.6 +/- 5.3 mm Hg), p = 0.047. The presence of nodules was combined with considerably increased risk of death, both in univariate analysis (HR 5.35, 95% CI: 1.16-24.7, p = 0.03) and in multivariate analysis (HR 6.98, 95% CI: 1.41-34.59, p = 0.02). Ground-glass opacifications correlated neither with haemodynamic nor functional indexes, and were of no prognostic significance. CONCLUSIONS: The presence of centrilobular nodules in lung HRCT scans of IPAH patients was combined with more severe haemodynamic compromise and was an independent negative prognostic indicator.

Characteristics and prognosis of patients with decompensated right ventricular failure during the course of pulmonary hypertension.

BACKGROUND: New therapies for pulmonary arterial hypertension have prolonged survival but simultaneously increased the number of hospital admissions because of decompensated right heart failure (DRHF). The optimal approach in DRHF has not been established yet. AIM: Analysis of clinical course of DRHF in a group of patients with pulmonary hypertension treated in a single referral centre. METHODS: We retrospectively analysed 60 episodes of DRHF in 37 patients (29 females, mean age 44+/-17 years) with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension admitted to our hospital between 2005 and 2007. We assessed the cause of decompensation, vital signs at admission, functional class and laboratory values. We classified all episodes into four haemodynamic profiles using the value of systolic blood pressure together with presence of peripheral perfusion abnormalities (profile cold vs. warm) and symptoms of venous congestion (profile wet vs. dry). Primary end-point was in-hospital mortality. RESULTS: The most common causes of DRHF were infection (27%), drug noncompliance (20%), and pulmonary embolism (3%). In 48% no causative factor was indentified. There were 19 (32%) in-hospital deaths. The highest mortality was observed among patients with connective tissue disease (61%). The haemodynamic profile 'warm-wet' was the most common (48%) and the profile 'cold-dry' was the rarest but was associated with a 100% mortality. Patients who died had higher value of functional class (3.84+/-0.38 vs. 3.51+/-0.55, p=0.01) and higher activity of aspartate transaminase (61+/-61 vs. 42+/-78 U/l, p=0.02) compared with those who survived. In multivariate analysis higher dopamine dose (RR 2.0/1 microg/kg/min, 95% CI 1.00-5.00, p <0.001) was an independent factor of in-hospital death. In contrast 'rescue therapy' with iloprost or treprostinil decreased mortality (RR 0.09, 95% CI 0.01-0.99, p=0.04). Mortality in patients receiving dopamine was higher (60 vs. 18%, p=0.001) than in patients treated without dopamine. CONCLUSION: Mortality in patients with pulmonary hypertension and DRHF remains very high and seems to be related to haemodynamic profile on admission. The newly introduced therapy with parenteral prostanoids may be more beneficial than dopamine infusion.

[Infective endocarditis in a patient with multiple myeloma. A case report]. / Infekcyjne zapalenie wsierdzia w przebiegu szpiczaka mnogiego -- trudnosci diagnostyczno-terapeutyczne. Opis przypadku.

A case of a 59 year old male with infective endocarditis is presented. Antibiotic therapy seemed effective, however, inflammation laboratory parameters increased two weeks after clinical improvement and body temperature normalisation. Subsequent extensive laboratory investigations revealed multiple myeloma. The patient underwent successful aortic valve replacement and received pharmacological therapy for multiple myeloma. Difficulties in diagnosing and treatment of patients with infective endocarditis who have other concomitant diseases, are discussed.