Biomarkers related to silicosis and pulmonary function in individuals exposed to silica.

BACKGROUND: The identification of markers that can facilitate the early diagnosis of silicosis has remained challenging. We evaluated the association of inflammatory markers with the presence of silicosis and lung function impairment in individuals exposed to silica. METHODS: Individuals exposed and not exposed to silica were assessed by occupational history, clinical findings, lung function, chest imaging findings, and inflammatory markers. RESULTS: Among 297 men evaluated, 51 were unexposed controls (G1), 149 were exposed to silica without silicosis (G2), and 97 were exposed to silica with silicosis (G3). Inflammatory marker levels were higher in G3 than in G2 and G1. Platelet/lymphocyte ratio (PLR), lactate dehydrogenase (LDH), soluble tumor necrosis factor II (sTNFRII), and macrophage inflammatory protein-4 (MIP-4) were associated with silicosis, and LDH, neutrophil/lymphocyte ratio (NLR), sTNFRII, monocyte chemoattractant protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and fibrinogen were negatively associated with lung function. CONCLUSION: Blood inflammatory markers are associated with silicosis and impaired lung function.

Work-related asthma consequences on socioeconomic, asthma control, quality of life, and psychological status compared with non-work-related asthma: A cross-sectional study in an upper-middle-income country.

BACKGROUND: Work-related asthma (WRA) is the most prevalent occupational respiratory disease, and it has negative effects on socioeconomic standing, asthma control, quality of life, and mental health status. Most of the studies on WRA consequences are from high-income countries; there is a lack of information on these effects in Latin America and in middle-income countries. METHODS: This study compared socioeconomic, asthma control, quality of life, and psychological outcomes among individuals diagnosed with WRA and non-work-related asthma (NWRA) in a middle-income country. Patients with asthma, related and not related to work, were interviewed using a structured questionnaire to assess their occupational history and socioeconomic conditions, and with questionnaires to assess asthma control (Asthma Control Test and Asthma Control Questionnaire-6), quality of life (Juniper's Asthma Quality of Life Questionnaire), and presence of anxiety and depression symptoms (Hospital Anxiety and Depression Scale). Each patient's medical record was reviewed for exams and use of medication, and comparisons were made between individuals with WRA and NWRA. RESULTS: The study included 132 patients with WRA and 130 with NWRA. Individuals with WRA had worse socioeconomic outcomes, worse asthma control, more quality-of-life impairment, and a higher prevalence of anxiety and depression than individuals with NWRA. Among individuals with WRA, those who had been removed from occupational exposure had a worse socioeconomic impact. CONCLUSIONS: Consequences on socioeconomic, asthma control, quality of life, and psychological status are worse for WRA individuals when compared with NWRA.

Mesothelioma in situ with regressive malignant pleural effusion and an unexpected evolution: A case report.

Malignant pleural mesothelioma (MPM) is an aggressive neoplasm that originates from hyperplasia and metaplasia of the mesothelial cells that cover the pleural cavity. Previous exposure to asbestos is the main risk factor. Since MPM is often diagnosed at an advanced stage with rapid evolution and resistance to treatment, it is associated with an unfavorable outcome. Mesothelioma in situ (MIS) has been postulated as a preinvasive phase of MPM; however, its diagnostic criteria have been defined only recently. Diagnosis of MIS may represent an opportunity for early therapies with better results, but the optimal approach has not been defined thus far. Here, we report on a case of a 74-year-old man with right-sided pleural effusion and a previous history of occupational exposure to asbestos for 9 years who was diagnosed with MIS after a latency of 36 years. During follow-up, spontaneous disease regression was observed 5 months after the initial diagnosis; however, it recurred in the form of invasive epithelioid MPM. There is a paucity of literature on MIS and its evolution; however, our case provides relevant knowledge of this unusual behavior, which is important to define follow-up and therapeutic strategies for future cases.

Burnt sugarcane harvesting is associated with acute renal dysfunction.

Sugarcane harvesting has been associated with an epidemic of chronic kidney disease in Central America mainly affecting previously healthy young workers. Repeated episodes of acute kidney dysfunction are hypothesized to be one of the possible mechanisms for this phenomenon. Therefore, this exploratory study aimed to assess the acute effects of burnt sugarcane harvesting on renal function among 28 healthy non-African Brazilian workers. Urine and blood samples were collected at the beginning and at the end of the harvesting season and before and at the end of a harvesting workday. All individuals decreased their estimated glomerular filtration rate by ∼20% at the end of the daily shift, and 18.5% presented with serum creatinine increases consistent with acute kidney injury. Those changes were associated with increased serum creatine phosphokinase (a known marker for exertional rhabdomyolysis) and oxidative stress-associated malondialdehyde levels, increased peripheral blood white cell counts, decreased urinary and serum sodium, decreased calculated fractional sodium excretion, and increased urine density. Thus, burnt sugarcane harvesting caused acute renal dysfunction in previously healthy workers. This was associated with a combination of dehydration, systemic inflammation, oxidative stress, and rhabdomyolysis.

Aging of the lungs in asymptomatic lifelong nonsmokers: findings on HRCT.

PURPOSE: To report lung parenchymal findings on high-resolution computed tomography (HRCT) in a population of asymptomatic, never-smoker urban dwellers aged 65 years and older. MATERIALS AND METHODS: After institutional approval, asymptomatic older patients from the Geriatrics Outpatient Clinic aged 65 years and older (older group) and healthy volunteers aged 30-50 years (younger group) were invited to participate in the study. Asymptomatic, never-smoker subjects considered free of relevant disease after spirometry and echocardiography underwent chest HRCT. Three researchers reviewed every scan, noting the absence/presence and distribution of pre-specified parenchymal findings. Statistical comparisons between groups were performed using appropriate tests with the aid of software. RESULTS: Forty-seven older and 24 younger subjects were included in this analysis. A higher proportion of women and a longer history of urban dwelling were present in the older group. Parenchymal findings were more prevalent in the older group (78.7 vs. 25% in the younger group; p < 0.001). Parenchymal bands (59.6 vs. 25%; p = 0.007), ground-glass opacities (25.5 vs. 0%; p = 0.006), and septal lines (21.3 vs. 0%; p = 0.013) were more prevalent in the elderly. When only subjects aged 75 years and older were considered as the older group, micronodules, reticular opacities, cysts, and bronchiectases (19.1 vs. 0 % for all comparisons; p = 0.04) were also more frequently found among the elderly. CONCLUSION: Parenchymal bands, ground-glass opacities, septal lines, bronchiectasis, micronodules, reticular opacities, and lung cysts were more prevalent among the elderly.

Selectins and platelet-derived growth factor (PDGF) in schistosomiasis-associated pulmonary hypertension.

PURPOSE: The aim of this study was to evaluate the expression profiles of the relevant selectins and PDGF in schistosomiasis-associated pulmonary hypertension. METHODOLOGY: Patients with three distinct clinical profiles were enrolled in the study: IPAH(n = 11), schistosomiasis-associated PH (Sch-PH))(n = 13), and schistosomiasis without PH (Sch) (n = 13). Healthy volunteers, were recruited as a control group(n = 13). Echocardiography was performed in all groups, and the PH patients underwent right heart catheterization. Plasma soluble adhesion molecules E- and P-Selectin, PDGF-AB, PDGF-BB were determined by ELISA. RESULTS: E-selectin was significantly increased in the IPAH group compared with the other groups [the control, Sch + PH and Sch groups) (p < 0.001) (Fig. 2)]. P-selectin was lower in Sch (20.2 + 8.9 × 103 pg/mL) as compared to the control, (43 16.8 × 103 pg/mL), IPAH (35.8 7.8 × 103 pg/mL), and Sch + PH (36.8 ± 15.7 × 103 pg/mL) (p = 0.005) groups. Serum PDGF-BB levels were higher in the control group (8.9 ± 4.8 × 103 pg/mL) compared with the IPAH (3.7 ± 2.17 × 103 pg/mL), Sch + PH (5.2 ± 3.7 × 103 pg/mL) and Sch (2.4 ± 1.7 × 103 pg/mL) groups (p < 0.05). PDGF-AB levels were also higher in the control group (25.6 ± 8.6 × 103 pg/mL), compared with the other three groups, being the Sch group the one with lower serum levels of this marker (11.4 ± 8.6 × 103 pg/mL) (p = 0.006). CONCLUSIONS: In conclusion, vascular inflammation in schistosomiasis, with or without PH, is different from IPAH suggesting distinct pathophysiological mechanisms associated with the development of pulmonary hypertension.

Recognition, diagnosis, and operability assessment of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Early recognition and diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is crucial for improving prognosis and reducing the disease burden. Established clinical practice guidelines describe interventions for the diagnosis and evaluation of CTEPH, yet limited insight remains into clinical practice variation and barriers to care. The CTEPH global cross-sectional scientific survey (CLARITY) was developed to gather insights into the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the recognition and diagnosis of CTEPH and the referral and evaluation of these patients. The survey was offered to hospital-based medical specialists through Scientific Societies and other medical organizations, from September 2021 to May 2022. Response data from 353 physicians showed that self-reported awareness of CTEPH increased over the past 10 years among 96% of respondents. Clinical practices in acute pulmonary embolism (PE) follow-up and CTEPH diagnosis differed among respondents. While 50% of respondents working in a nonexpert center reported to refer patients to an expert pulmonary hypertension/CTEPH center when CTEPH is suspected, 51% of these physicians did not report referral of patients with a confirmed diagnosis for further evaluation. Up to 50% of respondents involved in the evaluation of referred patients have concluded a different operability status than that indicated by the referring center. This study indicates that early diagnosis and timely treatment of CTEPH is challenged by suboptimal acute PE follow-up and patient referral practices. Nonadherence to guideline recommendations may be impacted by various barriers to care, which were shown to vary by geographical region.

Treatment and management of chronic thromboembolic pulmonary hypertension (CTEPH): A global cross-sectional scientific survey (CLARITY).

Advances in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) over the past decade changed the disease landscape, yet global insight on clinical practices remains limited. The CTEPH global cross-sectional scientific survey (CLARITY) aimed to gather information on the current diagnosis, treatment, and management of CTEPH and to identify unmet medical needs. This paper focuses on the treatment and management of CTEPH patients. The survey was circulated to hospital-based medical specialists through Scientific Societies and other medical organizations from September 2021 to May 2022. The majority of the 212 respondents involved in the treatment of CTEPH were from centers performing up to 50 pulmonary endarterectomy (PEA) and/or balloon pulmonary angioplasty (BPA) procedures per year. Variation was observed in the reported proportion of patients deemed eligible for PEA/BPA, as well as those that underwent the procedures, including multimodal treatment and subsequent follow-up practices. Prescription of pulmonary arterial hypertension-specific therapy was reported for a variable proportion of patients in the preoperative setting and in most nonoperable patients. Reported use of vitamin K antagonists and direct oral anticoagulants was similar (86% vs. 82%) but driven by different factors. This study presents heterogeneity in treatment approaches for CTEPH, which may be attributed to center-specific experience and region-specific barriers to care, highlighting the need for new clinical and cohort studies, comprehensive clinical guidelines, and continued education.

Update on pulmonary arteriovenous malformations.

This review aimed to provide an overview of pulmonary arteriovenous malformations, including the major clinical and radiological presentations, investigation, and treatment algorithm of the condition. The primary etiology of pulmonary arteriovenous malformations is hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, with mutations in the ENG gene on chromosome 9 (HHT type 1) or in the ACVRL1/ALK1 complex (HHT type 2). Epistaxis should always be evaluated when repeated, when associated with anemia, and in some cases of hypoxemia. In the investigation, contrast echocardiography and chest CT are essential for evaluating this condition. Embolization is the best treatment choice, especially for correction in cases of hypoxemia or to avoid systemic infections. Finally, disease management was addressed in special conditions such as pregnancy. CT follow-up should be performed every 3-5 years, depending on the size of the afferent and efferent vessels, and antibiotic prophylactic care should always be oriented. Ultimately, knowledge of the disease by health professionals is a crucial point for the early diagnosis of these patients in clinical practice, which can potentially modify the natural course of the disease.

An Evaluation of the Impact of Air Pollution on the Lung Functions of High School Students Living in a Ceramic Industrial Park Zone.

Santa Gertrudes (SG) and Rio Claro (RC), Sao Paulo, Brazil, are located in a ceramic industrial park zone, and their particulate matter with an aerodynamic diameter of less than 10 µm (PM10) concentration levels has been among the highest in recently monitored cities in Brazil. Local PM10 was mostly composed of silica. A cross-sectional study was designed to evaluate the lung functions of public high school students in SG, RC, and São Pedro (SP) (control location), Brazil, in 2018. The prevalence of asthma, mean PM10, FVC (forced vital capacity), and FEV1 (forced expiratory volume in the first second) were compared between the locations, and regression analyses were performed. A total of 450 students were included (SG: 158, RC: 153, and SP: 139). The mean FVC% (SG: 95.0% ± 11.8%, RC: 98.8% ± 12.9%, SP: 102.4% ± 13.8%, p < 0.05), the mean FEV1% (SG: 95.7% ± 10.4%, RC: 99.7% ± 12.0%, SP: 103.2% ± 12.0%, p < 0.05) and the mean PM10 (SG: 77.75 ± 38.08 µg/m3, RC: 42.59 ± 23.46 µg/m3, SP: 29.52 ± 9.87 µg/m3, p < 0.01) differed between locations. In regression models, each increase in PM10 by 10 µg/m3 was associated with a decrease in FVC% by 1.10% (95% CI 0.55%-1.65%) and a decrease in FEV1% by 1.27% (95% CI 0.75%-1.79%). Exposure to high levels of silica-rich environmental PM10 was found to be associated with lower FVC and FEV1.

Brazilian Thoracic Society recommendations for the diagnosis and treatment of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious and debilitating disease caused by occlusion of the pulmonary arterial bed by hematic emboli and by the resulting fibrous material. Such occlusion increases vascular resistance and, consequently, the pressure in the region of the pulmonary artery, which is the definition of pulmonary hypertension. The increased load imposed on the right ventricle leads to its progressive dysfunction and, finally, to death. However, CTEPH has a highly significant feature that distinguishes it from other forms of pulmonary hypertension: the fact that it can be cured through treatment with pulmonary thromboendarterectomy. Therefore, the primary objective of the management of CTEPH should be the assessment of patient fitness for surgery at a referral center, given that not all patients are good candidates. For the patients who are not good candidates for pulmonary thromboendarterectomy, the viable therapeutic alternatives include pulmonary artery angioplasty and pharmacological treatment. In these recommendations, the pathophysiological bases for the onset of CTEPH, such as acute pulmonary embolism and the clinical condition of the patient, will be discussed, as will the diagnostic algorithm to be followed and the therapeutic alternatives currently available.

Lung diffusing capacity relates better to short-term progression on HRCT abnormalities than spirometry in mild asbestosis.

BACKGROUND: Pulmonary function tests (PFT), particularly spirometry and lung diffusing capacity for carbon monoxide (DL(CO) ), have been considered useful methods for the detection of the progression of interstitial asbestos abnormalities as indicated by high-resolution computed tomography (HRCT). However, it is currently unknown which of these two tests correlates best with anatomical changes over time. METHODS: In this study, we contrasted longitudinal changes (3-9 years follow-up) in PFTs at rest and during exercise with interstitial abnormalities evaluated by HRCT in 63 ex-workers with mild-to-moderate asbestosis. RESULTS: At baseline, patients presented with low-grade asbestosis (Huuskonen classes I-II), and most PFT results were within the limits of normality. In the follow-up, most subjects had normal spirometry, static lung volumes and arterial blood gases. In contrast, frequency of DL(CO) abnormalities almost doubled (P < 0.05). Twenty-three (36.5%) subjects increased the interstitial marks on HRCT. These had significantly larger declines in DL(CO) compared to patients who remained stable (0.88 vs. 0.31 ml/min/mm Hg/year and 3.5 vs. 1.2%/year, respectively; P < 0.05). In contrast, no between-group differences were found for the other functional tests, including spirometry (P > 0.05). CONCLUSIONS: These data demonstrate that the functional consequences of progression of HRCT abnormalities in mild-to-moderate asbestosis are better reflected by decrements in DL(CO) than by spirometric changes. These results might have important practical implications for medico-legal evaluation of this patient population.

Work-related asthma.

Work-related asthma (WRA) is highly prevalent in the adult population. WRA includes occupational asthma (OA), which is asthma caused by workplace exposures, and work-exacerbated asthma (WEA), also known as work-aggravated asthma, which is preexisting or concurrent asthma worsened by workplace conditions. In adults, the estimated prevalence of OA is 16.0%, whereas that of WEA is 21.5%. An increasing number of chemicals used in industrial production, households, and services are associated with the incidence of adult-onset asthma attributable to exposure to chemicals. This review article summarizes the different types of WRA and describes diagnostic procedures, treatment, prevention, and approaches to patient management. It is not always easy to distinguish between OA and WEA. It is important to establish a diagnosis (of sensitizer-/irritant-induced OA or WEA) in order to prevent worsening of symptoms, as well as to prevent other workers from being exposed, by providing early treatment and counseling on social security and work-related issues.

Knowledge of and attitudes toward the WHO MPOWER policies to reduce tobacco use at the population level: a comparison between third-year and sixth-year medical students.

OBJECTIVE: To evaluate third- and sixth-year medical students in Brazil in terms of their knowledge of and attitudes toward the WHO MPOWER policies to reduce tobacco use. METHODS: The WHO Global Health Professions Student Survey was applied in five cohorts of medical students evaluated in their third and sixth years of medical school, between 2008 and 2015. Comparisons were drawn between the two years of medical school in terms of the proportions of students who experimented with or used tobacco products in the last 30 days prior to the survey; knowledge of and compliance with smoke-free policies on the university campus; formal training on smoking cessation strategies; and self-recognition as role models for patients/society. RESULTS: Of the 943 students who completed the survey, approximately 6% had smoked cigarettes in the last 30 days prior to the survey. Comparing the third and sixth years of medical school, we observed a significant increase in the proportion of students who were knowledgeable about smoking cessation strategies (22.74% vs. 95.84%; p < 0.001) and in that of those who recognized their role as models for patients/society (84.5% vs. 89.7%; p = 0.023). Student knowledge of the smoking policies on the university campus was associated with an increase in self-recognition as role models (adjusted absolute difference = 6.7%; adjusted p = 0.050). CONCLUSIONS: Knowledge of smoking cessation strategies and self-recognition as role models for patients/society increase over the course of medical school and are associated with the implementation of smoke-free policies.

Chronic thromboembolic pulmonary hypertension: the impact of advances in perioperative techniques in patient outcomes.

OBJECTIVES: Pulmonary endarterectomy (PEA) is the gold standard treatment for chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed at reporting outcomes of CTEPH patients undergoing PEA within 10 years, focusing on advances in anesthetic and surgical techniques. METHODS: We evaluated 102 patients who underwent PEA between January 2007 and May 2016 at the Instituto do Coração do Hospital das Clínicas da Universidade de São Paulo. Changes in techniques included longer cardiopulmonary bypass, heating, and cooling times and mean time of deep hypothermic circulatory arrest and shortened reperfusion time. Patients were stratified according to temporal changes in anesthetic and surgical techniques: group 1 (January 2007-December 2012), group 2 (January 2013-March 2015), and group 3 (April 2015-May 2016). Clinical outcomes were any occurrence of complications during hospitalization. RESULTS: Groups 1, 2, and 3 included 38, 35, and 29 patients, respectively. Overall, 62.8% were women (mean age, 49.1 years), and 65.7% were in New York Heart Association functional class III-IV. Postoperative complications were less frequent in group 3 than in groups 1 and 2: surgical complications (10.3% vs. 34.2% vs. 31.4%, p=0.035), bleeding (10.3% vs. 31.5% vs. 25.7%, p=0.047), and stroke (0 vs. 13.2% vs. 0, p=0.01). Between 3 and 6 months post-discharge, 85% were in NYHA class I-II. CONCLUSION: Improvements in anesthetic and surgical procedures were associated with better outcomes in CTEPH patients undergoing PEA during the 10-year period.

Environmental air pollution: respiratory effects.

Environmental air pollution is a major risk factor for morbidity and mortality worldwide. Environmental air pollution has a direct impact on human health, being responsible for an increase in the incidence of and number of deaths due to cardiopulmonary, neoplastic, and metabolic diseases; it also contributes to global warming and the consequent climate change associated with extreme events and environmental imbalances. In this review, we present articles that show the impact that exposure to different sources and types of air pollutants has on the respiratory system; we present the acute effects-such as increases in symptoms and in the number of emergency room visits, hospitalizations, and deaths-and the chronic effects-such as increases in the incidence of asthma, COPD, and lung cancer, as well as a rapid decline in lung function. The effects of air pollution in more susceptible populations and the effects associated with physical exercise in polluted environments are also presented and discussed. Finally, we present the major studies on the subject conducted in Brazil. Health care and disease prevention services should be aware of this important risk factor in order to counsel more susceptible individuals about protective measures that can facilitate their treatment, as well as promoting the adoption of environmental measures that contribute to the reduction of such emissions.

Update on the Treatment of Pulmonary Arterial Hypertension. / Atualização no Tratamento da Hipertensão Arterial Pulmonar.

In the last decades, important advances have been made in the treatment of pulmonary arterial hypertension (PAH), a severe, progressive, incurable, and potentially fatal disease. For an adequate therapy, correct hemodynamic diagnosis and etiology classification are fundamental. Many etiologies - rheumatic disease, portal hypertension, congenital heart diseases, schistosomiasis - require specific measures, in addition to drug therapy for PAH. The specific therapy for PAH is based on medications that act on three pathophysiological pathways - prostacyclin, endothelin, and nitric oxide pathways. These drugs have multiple presentations (oral, intravenous, subcutaneous, and inhaled) and have changed the history of PAH. This review presents an overview of drug therapy strategies and different forms and peculiarities of PAH.

Muitos avanços ocorreram nas últimas décadas na terapêutica da hipertensão arterial pulmonar (HAP), uma doença grave, progressiva, incurável e potencialmente fatal. Para seu tratamento adequado, são fundamentais o diagnóstico hemodinâmico e a classificação de sua etiologia, em que várias delas (colagenoses, hipertensão portal, cardiopatia congênitas, esquistossomose) requerem medidas específicas, além do tratamento farmacológico característico para HAP. O tratamento com fármacos-alvo para HAP baseia-se em produtos farmacêuticos que interferem em três vias fisiopatológicas moleculares: da prostaciclina, da endotelina e do óxido nítrico. Tais fármacos apresentam múltiplas apresentações (oral, endovenosa, subcutânea e inalatória) e mudaram a história da HAP. Essas medicações e suas estratégias de uso, assim como particularidades das diferentes formas de HAP, são o foco desta revisão.

Cardiopulmonary manifestations of hepatosplenic schistosomiasis.

BACKGROUND: Schistosomiasis is a highly prevalent disease with >200 million infected people. Pulmonary hypertension is one of the pulmonary manifestations in this disease, particularly in its hepatosplenic presentation. The aim of this study was to determine the prevalence of pulmonary hypertension in schistosomiasis patients with the hepatosplenic form of the disease. METHODS AND RESULTS: All patients with hepatosplenic schistosomiasis followed up at the gastroenterology department of our university hospital underwent echocardiographic evaluation to search for pulmonary hypertension. Patients presenting with systolic pulmonary artery pressure >40 mm Hg were further evaluated through right heart catheterization. Our study showed an 18.5% prevalence of patients with elevated systolic pulmonary artery pressure at echocardiography. Invasive hemodynamics confirmed the presence of pulmonary hypertension in 7.7% (95% confidence interval, 3.3 to 16.7) of patients, with a prevalence of precapillary (arterial) pulmonary hypertension of 4.6% (95% confidence interval, 1.5 to 12.7). CONCLUSIONS: Our study reinforces the role of echocardiography as a screening tool in the investigation of pulmonary hypertension, together with the need for invasive monitoring for a proper diagnosis. We conclude that hepatosplenic schistosomiasis may account for one of the most prevalent forms of pulmonary hypertension worldwide, justifying the development of further studies to evaluate the effect of specific pulmonary hypertension treatment in this particular form of the disease.

Lung Cavities in Chronic Thromboembolic Pulmonary Hypertension.

OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) is a unique form of pulmonary hypertension (PH) that arises from obstruction of the pulmonary vessels by recanalized thromboembolic material. CTEPH has a wide range of radiologic presentations. Commonly, it presents as main pulmonary artery enlargement, peripheral vascular obstructions, bronchial artery dilations, and mosaic attenuation patterns. Nevertheless, other uncommon presentations have been described, such as lung cavities. These lesions may be solely related to chronic lung parenchyma ischemia but may also be a consequence of concomitant chronic infectious conditions. The objective of this study was to evaluate the different etiologies that cause lung cavities in CTEPH patients. METHODS: A retrospective data analysis of the medical records of CTEPH patients in a single reference PH center that contained or mentioned lung cavities was conducted between 2013 and 2016. RESULTS: Seven CTEPH patients with lung cavities were identified. The cavities had different sizes, locations, and wall thicknesses. In two patients, the cavities were attributed to pulmonary infarction; in 5 patients, an infectious etiology was identified. CONCLUSION: Despite the possibility of being solely associated with chronic lung parenchyma ischemia, most cases of lung cavities in CTEPH patients were associated with chronic granulomatous diseases, reinforcing the need for active investigation of infectious agents in this setting.

Shear stress-exposed pulmonary artery endothelial cells fail to upregulate HSP70 in chronic thromboembolic pulmonary hypertension.

The pathophysiological mechanisms underlying chronic thromboembolic pulmonary hypertension (CTEPH) are still unclear. Endothelial cell (EC) remodeling is believed to contribute to this pulmonary disease triggered by thrombus and hemodynamic forces disbalance. Recently, we showed that HSP70 levels decrease by proatherogenic shear stress. Molecular chaperones play a major role in proteostasis in neurological, cancer and inflammatory/ infectious diseases. To shed light on microvascular responses in CTEPH, we characterized the expression of molecular chaperones and annexin A2, a component of the fibrinolytic system. There is no animal model that reproduces microvascular changes in CTEPH, and this fact led us to isolated endothelial cells from patients with CTEPH undergoing pulmonary endarterectomy (PEA). We exposed CTEPH-EC and control human pulmonary endothelial cells (HPAEC) to high- (15 dynes/cm2) or low- (5 dynes/cm2) shear stress. After high-magnitude shear stress HPAEC upregulated heat shock protein 70kDa (HSP70) and the HSP ER paralogs 78 and 94kDa glucose-regulated protein (GRP78 and 94), whereas CTEPH-ECs failed to exhibit this response. At static conditions, both HSP70 and HSP90 families in CTEPH-EC are decreased. Importantly, immunohistochemistry analysis showed that HSP70 expression was downregulated in vivo, and annexin A2 was upregulated. Interestingly, wound healing and angiogenesis assays revealed that HSP70 inhibition with VER-155008 further impaired CTEPH-EC migratory responses. These results implicate HSP70 as a novel master regulator of endothelial dysfunction in type 4 PH. Overall, we first show that global failure of HSP upregulation is a hallmark of CTEPH pathogenesis and propose HSP70 as a potential biomarker of this condition.