End-of-Life and Palliative Care Issues for Patients Living with Pulmonary Arterial Hypertension: Barriers and Opportunities.

Pulmonary arterial hypertension (PAH) is a progressive, incurable disease that results in significant symptom burden, health care utilization, and eventually premature death. Despite the advancements made in treatment and management strategies, survival has remained poor. End-of-life care is a challenging issue in management of PAH, especially when patients are in younger age group. End-of-life care revolves around symptom palliation and reducing psychosocial disease burden for a dying patient and entails advanced care planning that are often challenging. Thus, support from palliative care specialist becomes extremely important in these patients. Early introduction to palliative care in patients with high symptom burden and psychosocial suffering is suggested. Despite of the benefits of an early intervention, palliative care remains underutilized in patients with PAH, and this significantly raises issues around end-of-life care in PAH. In this review, we will discuss the opportunities offered and the existing barriers in addressing high symptom burden and end-of-life care issues. We will focus on the current evidence, identify areas for future research, and provide a call-to-action for better guidance to PAH specialists in making timely, appropriate interventions that can help mitigate end-of-life care issues.

Idiopathic pulmonary fibrosis and pulmonary hypertension: Heracles meets the Hydra.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease where the additional presence of pulmonary hypertension (PH) reduces survival. In particular, the presence of coexistent pulmonary vascular disease in patients with advanced lung parenchymal disease results in worse outcomes than either diagnosis alone. This is true with respect to the natural histories of these diseases, outcomes with medical therapies, and even outcomes following lung transplantation. Consequently, there is a striking need for improved treatments for PH in the setting of IPF. In this review, we summarize existing therapies from the perspective of molecular mechanisms underlying lung fibrosis and vasoconstriction/vascular remodelling and discuss potential future targets for pharmacotherapy. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc.

Emerging Mechanisms of Pulmonary Vasoconstriction in SARS-CoV-2-Induced Acute Respiratory Distress Syndrome (ARDS) and Potential Therapeutic Targets.

The 1918 influenza killed approximately 50 million people in a few short years, and now, the world is facing another pandemic. In December 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of a respiratory illness termed coronavirus disease 2019 (COVID-19) and rapidly spread to cause the worst pandemic since 1918. Recent clinical reports highlight an atypical presentation of acute respiratory distress syndrome (ARDS) in COVID-19 patients characterized by severe hypoxemia, an imbalance of the renin-angiotensin system, an increase in thrombogenic processes, and a cytokine release storm. These processes not only exacerbate lung injury but can also promote pulmonary vascular remodeling and vasoconstriction, which are hallmarks of pulmonary hypertension (PH). PH is a complication of ARDS that has received little attention; thus, we hypothesize that PH in COVID-19-induced ARDS represents an important target for disease amelioration. The mechanisms that can promote PH following SARS-CoV-2 infection are described. In this review article, we outline emerging mechanisms of pulmonary vascular dysfunction and outline potential treatment options that have been clinically tested.

Pulmonary arterial hypertension in breast cancer patients on HER2-targeted therapy: a review of FDA Adverse Events Reporting System data.

This letter highlights a rare association of anti-HER2 cancer therapy with development of pulmonary arterial hypertension, based on a review of data from the FDA https://bit.ly/2X90xDu.

Thyroid Dysfunction in Patients with Pulmonary Artery Hypertension (PAH): The Effect of Therapies Affecting the Prostanoid Pathway.

INTRODUCTION: Epoprostenol, a synthetic prostaglandin I2 (PGI2) analog, has been the mainstay of treatment for severe pulmonary arterial hypertension (PAH) for the last two decades. Treprostinil, another synthetic prostaglandin analog, and selexipag, an oral selective Inositol Phosphate (IP) prostacyclin receptor agonist, have also been approved for treatment of PAH. Prostacyclin and its analogs cause a variety of side effects in patients with PAH; however, thyroid dysfunction is rarely reported. METHODS: After treating an index case of thyroid dysfunction occurring after initiation of epoprostenol, we reviewed our databases of PAH patients treated with epoprostenol, treprostinil or selexipag to identify the occurrence of this association. RESULTS: We identified six cases of thyroid dysfunction in our cohort: five after initiation of an intravenous prostacyclin (epoprostenol) and one after initiation of an oral prostacyclin receptor agonist (selexipag). Four of the patients presented with hyperthyroidism and two with a large autoimmune goiter. Graves' disease was seen in three patients, Hashimoto's disease in two patients and thyrotoxicosis in one patient. CONCLUSION: Therapy with medications targeting the prostacyclin pathway is a potential risk factor for the development of symptomatic thyroid disease.

Palliative care in pulmonary arterial hypertension: an underutilised treatment.

Pulmonary arterial hypertension (PAH) is a condition characterised by increased pulmonary vascular resistance which can lead to right heart failure and premature death. It imposes a significant burden on patients' lives, affecting their physical, emotional and social wellbeing. Pharmacological therapies are the mainstay of treatment; while they are not curative, they can alleviate patient suffering, improve quality of life and delay disease progression. Despite these therapies, disease progresses in a significant number of patients, who are faced with the debilitating symptoms of PAH and treatment adverse effects. Palliative care is focused on providing relief from symptoms caused by a chronic illness. Palliative care aims to improve the health-related quality of life for patients and families, and although it is deemed appropriate at any stage of disease, it is most helpful when explored early in the course of disease. Importantly, palliative care can be provided in concert with pharmacological treatment. Despite its potential benefits, palliative care is frequently underutilised. There is a paucity of clinical studies testing the impact of palliative care in PAH which prompted us to summarise the available evidence, recognise obstacles in its utilisation and identify areas for future research.

Pulmonary foreign body granulomatosis in a chronic user of powder cocaine.

We describe the case of a 33-year-old man, a chronic user of powder cocaine, who presented with dyspnea, fever, night sweats, and significant weight loss. Chest HRCT revealed centrilobular nodules, giving an initial impression of miliary tuberculosis. Therefore, he was started on an empirical, four-drug antituberculosis treatment regimen. Four weeks later, despite the tuberculosis treatment, he continued to have the same symptoms. We then performed transbronchial lung biopsy. Histopathological analysis of the biopsy sample revealed birefringent foreign body granuloma. A corroborative history of cocaine snorting, the presence of centrilobular nodules, and the foreign body-related histopathological findings led to a diagnosis of pulmonary foreign body granulomatosis. This report underscores the fact that pulmonary foreign body granulomatosis should be included in the differential diagnosis of clinical profiles resembling tuberculosis.

Pulmonary foreign body granulomatosis in a chronic user of powder cocaine / Granulomatose pulmonar de corpo estranho em um usuário crônico de cocaína em pó

ABSTRACT We describe the case of a 33-year-old man, a chronic user of powder cocaine, who presented with dyspnea, fever, night sweats, and significant weight loss. Chest HRCT revealed centrilobular nodules, giving an initial impression of miliary tuberculosis. Therefore, he was started on an empirical, four-drug antituberculosis treatment regimen. Four weeks later, despite the tuberculosis treatment, he continued to have the same symptoms. We then performed transbronchial lung biopsy. Histopathological analysis of the biopsy sample revealed birefringent foreign body granuloma. A corroborative history of cocaine snorting, the presence of centrilobular nodules, and the foreign body-related histopathological findings led to a diagnosis of pulmonary foreign body granulomatosis. This report underscores the fact that pulmonary foreign body granulomatosis should be included in the differential diagnosis of clinical profiles resembling tuberculosis.

RESUMO Descrevemos o caso de um homem de 33 anos de idade, usuário crônico de cocaína em pó, que apresentava dispneia, febre, sudorese noturna e perda de peso significativa. A TCAR de tórax revelou nódulos centrolobulares, dando uma impressão inicial de tuberculose miliar. Por isso, o paciente passou a receber tratamento empírico com quatro tuberculostáticos. Quatro semanas depois, apesar do tratamento antituberculose, o paciente continuou a apresentar os mesmos sintomas. Foi então realizada a biópsia pulmonar transbrônquica. A análise histopatológica da amostra obtida revelou granuloma de corpo estranho birrefringente. A história de uso de cocaína por inalação, a presença de nódulos centrolobulares e os achados histopatológicos de corpos estranhos confirmaram o diagnóstico de granulomatose pulmonar de corpo estranho. Este relato destaca o fato de que a granulomatose pulmonar de corpo estranho deve ser incluída no diagnóstico diferencial de perfis clínicos que se assemelham a tuberculose.

Pleural effusions in acute and chronic leukemia and myelodysplastic syndrome.

PURPOSE OF REVIEW: Pulmonary manifestations have been well described in leukemia, but pleural disease is less common. This review highlights pleural effusions in acute and chronic leukemia and myelodysplastic syndrome (MDS) based on the evidence to date. Diagnostic workup and recommendations for the management of these effusions are also outlined. RECENT FINDINGS: Pleural effusions in patients with leukemia are most often due to infection and to a lesser extent leukemic infiltration of the pleura. The prognostic implications of these effusions are unclear, but survival is most likely determined by the underlying malignancy and its response to treatment. New therapies have changed survival in these patients, and some of these treatments, such as tyrosine kinase inhibitors, have emerged as important causes for these effusions. Pleural interventions may be accomplished with few complications. SUMMARY: Pleural effusions may occur with acute and chronic leukemia and MDS. Infection remains the most common cause. Malignant pleural effusions tend to occur in advanced disease in chronic leukemia, but they can be seen at any time with acute leukemia and MDS. With standard precautions, pleural procedures may be performed safely in this population. In cases of unclear cause, pleural and bone marrow biopsy should be considered.

Aspergilloma formation in cavitary sarcoidosis.

Pulmonary cavitation is rather uncommon in patients with sarcoidosis, and aspergilloma is even more uncommon in such cases. Here, we present the case of a 63-year-old female patient with cavitary lung disease who had been under treatment for TB for 9 months. A diagnosis of pulmonary sarcoidosis was established based on the fiberoptic bronchoscopy finding of noncaseating granuloma. Treatment with corticosteroids led to a dramatic improvement in symptoms. While under treatment for sarcoidosis, the patient developed an aspergilloma. She presented immediate skin test reactivity to Aspergillus fumigatus, as well as positivity for A. fumigatus serum precipitins. This is the first reported case of aspergilloma formation in a patient with cavitary sarcoidosis in India.

Aspergilloma formation in cavitary sarcoidosis / Formação de uma aspergilloma em sarcoidose com cavitação

Pulmonary cavitation is rather uncommon in patients with sarcoidosis, and aspergilloma is even more uncommon in such cases. Here, we present the case of a 63-year-old female patient with cavitary lung disease who had been under treatment for TB for 9 months. A diagnosis of pulmonary sarcoidosis was established based on the fiberoptic bronchoscopy finding of noncaseating granuloma. Treatment with corticosteroids led to a dramatic improvement in symptoms. While under treatment for sarcoidosis, the patient developed an aspergilloma. She presented immediate skin test reactivity to Aspergillus fumigatus, as well as positivity for A. fumigatus serum precipitins. This is the first reported case of aspergilloma formation in a patient with cavitary sarcoidosis in India.

A cavitação pulmonar é rara em pacientes com sarcoidose, e o aspergiloma é ainda mais raro nestes casos. Apresentamos o caso de uma paciente de 63 anos com doença pulmonar cavitária em tratamento para a TB por 9 meses. Estabeleceu-se o diagnóstico de sarcoidose pulmonar com base nos achados de granuloma não-caseoso na fibrobroncoscopia. Houve grande melhora dos sintomas com o tratamento com corticosteroides. A paciente desenvolveu um aspergiloma durante o tratamento para a sarcoidose. Houve reação imediata ao teste cutâneo para Aspergillus fumigatus, assim como resultado positivo para precipitinas de A. fumigatus no soro. Este é o primeiro caso relatado de formação de aspergiloma em um paciente com sarcoidose com cavitação na Índia.

Frequency of familial occurrence in 164 patients with allergic bronchopulmonary aspergillosis.

BACKGROUND: Asthma is known to run in families. Allergic bronchopulmonary aspergillosis (ABPA) occurs predominantly in patients with asthma. However, there are only 6 reports of familial occurrence over a period of 35 years. OBJECTIVE: To determine the frequency of familial occurrence in 164 patients with ABPA diagnosed over a period of 22 years in one unit. METHODS: The 164 patients with ABPA were reviewed for the occurrence of familial ABPA. Symptomatic family members were evaluated for the presence of ABPA as well as allergic Aspergillus sinusitis (AAS). Allergic bronchopulmonary aspergillosis and AAS were diagnosed as per criteria established. RESULTS: Of the 164 patients with ABPA, familial occurrence was detected in 4 pairs of first degree relatives, 2 of whom were parent-child while the other 2 were siblings. Familial ABPA was seen in 4.9% of the total patients. Of these 8 patients seven had symptoms of rhinitis while 4 had sinusitis confirmed on computed tomography of paranasal sinuses. Allergic Aspergillus sinusitis was detected in 3 of these 4 patients. The fourth patient with sinusitis did not consent to surgery required to confirm the diagnosis. Five of our 8 patients, prior to referral, had received antituberculous therapy. All patients responded favourably to oral prednisolone. CONCLUSION: Familial occurrence was documented in 4.9% of the 164 patients with ABPA.

Bronchial anthracofibrosis and tuberculosis presenting as a middle lobe syndrome.

Bronchial anthracofibrosis, a clinical entity described less than a decade ago, is characterised by anthracotic pigmentation of the bronchial mucosa with multifocal bronchial lumen narrowing. The right middle lobe is predominantly involved and is frequently associated with tuberculosis. The condition is generally seen in non-smoking elderly ladies with a longstanding history of wood smoke exposure. A 65 year-old lady presented to us with a one-month history of dry cough. The chest radiograph revealed a middle lobe syndrome which was confirmed on computed tomography (CT) scanning. In addition, narrowing of the right middle lobe bronchus was seen. This raised the suspicion of a malignancy. Fibreoptic bronchoscopy revealed anthracotic pigmentation, and bronchial aspirate showed acid fast bacilli. Culture of the aspirate grew Mycobacterium tuberculosis. The patient responded to standard antituberculous treatment.