Effect of Obesity on Mortality in Pulmonary Hypertension-A Systematic Review and Meta-Analysis.

Obesity is reported to have a protective effect on mortality in pulmonary hypertension (PH), a phenomenon known as obesity paradox. However, the data are conflicting, with some studies showing decreased mortality while other studies found no effect of obesity on mortality. Therefore, we performed a systematic review and meta-analysis to examine whether there is an association between obesity and mortality in PH. Only patients with PH diagnosed by right heart catheterization were included. We also performed a sub-group analysis of subjects with pre-capillary PH only. A total of six studies met the inclusion criteria, with a sample size of 13,987 patients. Obese subjects had lower mortality compared to non-obese subjects in the combined pre- and post-capillary PH group (hazard ratio 0.79, 95% CI 0.66-0.95, p = 0.01). While obesity was associated with reduction in mortality in the pre-capillary PH group (hazard ratio 0.77, 95% CI 0.60 to 0.98, p = 0.03), this was not uniform across all studies.

Hypersensitivity Pneumonitis With and Without Autoimmune Features: A Clinical Comparative Analysis.

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) caused by an immunological reaction to repeated inhalational exposure to antigens. The etiology and exact immunopathology are poorly understood. Autoimmunity overlapping with HP has been described but the role of concomitant autoimmunity in the clinical course and outcome of the HP is not clearly established. In this study, we examined patients diagnosed with HP and compare them to patients with concomitant HP and autoimmunity. METHODS: Patients were retrospectively screened from a single-center ILD registry. Patients > 18 years with an established multidisciplinary diagnosis of HP were included in the study. Patients with HP without autoimmune features and patients with HP with autoimmune features (HPAF) were assessed. We compared the demographics, clinical characteristics, treatment, and outcomes between the two groups. We used a Cox proportional hazards model to compare lung transplant-free survival outcomes of patients with HPAF to those with non-HPAF HP patients. RESULTS: Of 73 patients with HP, 43 were diagnosed with HPAF. Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to non-HPAF HP patients [48.8 vs 23.3%, p = 0.028, Crude odds ratio (cOR) = 3.14]. Symptomatically, those with HPAF reported a higher prevalence of arthritis as compared to non-HPAF HP (20.9 vs 3.3%, p = 0.040, cOR = 7.68). No significant differences between pulmonary function tests, oxygen requirements, mortality, and lung transplantation rates were found between the two groups. There was no statistically significant difference in transplant-free survival (p = 0.836). CONCLUSION: Patients with HPAF had a higher echocardiographic probability of pulmonary hypertension as compared to patients with non-HPAF HP. The clinical characteristics and outcomes did not differ between the two groups and concomitant autoimmunity among the HP group did not portend a poorer prognosis.

Precapillary pulmonary arterial hypertension in a patient with Proteus syndrome.

Proteus syndrome is a rare progressive multisystem disorder characterized by asymmetric, disproportionate overgrowth of bone, skin, and other tissue types. Molecular pathogenesis has been identified as somatic activating mutations of the AKT1 gene. The presentation of Proteus syndrome is exceptionally variable. Respiratory complications include emphysematous lung disease and predisposition to pulmonary emboli, the latter of which is a significant source of mortality. Pulmonary hypertension due to longstanding hypoxic lung disease as well as chronic thromboembolic events has been observed in this population. In contrast, precapillary pulmonary arterial hypertension in the absence of chronic pulmonary emboli and parenchymal lung disease has not been described in the literature on patients with Proteus syndrome. We report such a case in a young patient with Proteus syndrome, reviewing subsequent management and emphasizing the need for a detailed investigation of dyspnea.

Pre-Existing Psychiatric Illness Is Associated With an Increased Risk of Delirium in Patients With Acute Respiratory Distress Syndrome.

BACKGROUND: Patients with acute respiratory distress syndrome (ARDS) are highly susceptible to developing delirium for a multitude of reasons. Previous studies have linked pre-existing depression with an increased risk of postoperative delirium in patients undergoing cardiac and non-cardiac surgery. However, the evidence regarding the association between pre-existing psychiatric illnesses and delirium in ARDS patients is unknown. In this study, we aim to determine the relationship between pre-existing psychiatric illness and the risk of development of delirium amongst ARDS patients. STUDY DESIGN AND METHODS: We performed a retrospective study of a mixed group of patients admitted to the intensive care unit (ICU) between January 2016 and December 2019 with a diagnosis of ARDS per the Berlin definition. The study group was divided into 2 cohorts: subjects with delirium and subjects without delirium. Comparison between the 2 groups was conducted to examine the impact of pre-existing psychiatric illnesses including major depressive disorder (MDD), generalized anxiety disorder (GAD), bipolar disorder, schizophrenia, or post-traumatic stress disorder. Multivariable logistic regression analysis was performed adjusting for benzodiazepine use, sedatives, analgesics, sequential organ failure assessment score, and corticosteroid use to determine the association between pre-existing psychiatric disorders and delirium. RESULTS: 286 patients with ARDS were identified; 124 (43%) of whom were diagnosed with ICU delirium. In patients diagnosed with ICU delirium, 49.2% were found to have preexisting psychiatric illnesses, compared to 34.0% without any preexisting psychiatric illness (OR = 1.94, P = 0.01). In a subgroup analysis of individual psychiatric illnesses, GAD and MDD were associated with the development of delirium (OR = 1.88, P = 0.04 and OR = 1.76, P = 0.05 respectively). INTERPRETATION: ARDS patients with preexisting psychiatric illnesses, particularly GAD and MDD are associated with an increased risk of developing ICU delirium. Clinicians should be aware of the effect of psychiatric co-morbidities on developing delirium in critically ill patients.

Macrophage activating syndrome causing decompensated right heart failure.

BACKGROUND: Macrophage activating syndrome (MAS) is a form of hemophagocytic lymphohistiocytosis (HLH), a rare complication of autoimmune disease that is characterized by cytokine storm and multiorgan failure. CASE SUMMARY: A 32-year-old male presented with acutely decompensated pulmonary arterial hypertension and right heart failure secondary to MAS. The patient was immediately started on inhaled and intravenous epoprostenol, vasopressors and dexamethasone and anakinra were administered. Despite the therapies given, the patient's condition continued to decline, and he was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Over a few days, his clinical condition improved, and he was decannulated from VA-ECMO and later transitioned oral treprositinil and was discharged home. Due to its non-specific clinical manifestations, the diagnosis of MAS depends on high clinical suspicion and initial laboratory work up such as thrombocytopenia, transaminitis, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, etc. In our patient, MAS led to decompensated Pulmonary Arterial Hypertension (PAH) leading to right heart failure that was refractory to inhaled and intravenous epoprostenol and vasopressors and required VA-ECMO as a bridge to recovery while his MAS was managed by anakinra and dexamethasone. CONCLUSION: MAS can result in acute decompensation of PAH and right heart failure. Besides RV failure management, immunosuppressants such as anakinra, etoposide, etc. should be utilized early in the management of MAS. In refractory right heart failure, VA-ECMO can be considered as a bridge to recovery. There is a paucity of literature supporting the utilization of VA-ECMO in the management of refractory right heart failure caused by MAS in adults and much of the data stems from pediatric studies. This case serves as a fine example of successful use of VA-ECMO in adult population.

COVID-19 infection and severe rhabdomyolysis.

Although patients with COVID-19 can have mild nonspecific myalgia and mild elevation of creatinine kinase levels, severe myalgia along with elevation of creatinine kinase levels >10 times the upper normal limit and dark-colored urine indicate an underlying severe rhabdomyolysis. This report describes a 60-year-old morbidly obese man who was found to have severe rhabdomyolysis, along with acute kidney injury, dark-colored urine, and a positive COVID-19 test. He had a prolonged hospital course requiring continuous renal replacement therapy, mechanical ventilation, and multiple vasopressors and eventually died of multiorgan failure. The management of severe rhabdomyolysis and COVID-19 is challenging, and fluid resuscitation should be done cautiously, monitoring for early signs of fluid overload.

Ustekinumab associated chronic eosinophilic pneumonia.

INTRODUCTION: Ustekinumab-induced eosinophilic pneumonia is rare and to our knowledge, this is the fifth reported case of such an entity. CASE STUDY: A 60-year-old female was admitted with worsening shortness of breath and a nonproductive cough for 4 months. Her past medical history was significant for Crohn's disease and psoriatic arthritis that was previously managed with adalimumab and switched to ustekinumab 2 months before symptoms. Initial diagnostic workup showed 10% peripheral eosinophilia and a CT chest showed numerous 5 mm nodules scattered throughout the lungs along with some peripheral reticulations. Her BAL fluid analysis showed abnormally high eosinophil count (67%), greatly limiting her potential diagnoses to eosinophilic pneumonia, EGPA, and tropical pulmonary eosinophilia (TPE). AEP typically causes more severe disease with a rapid onset, and there was low suspicion for TPE based on history, leaving EGPA and CEP. Based on her negative autoimmune serology, a negative biopsy of the nasal mucosa (no vasculitis/granulomata or eosinophils), and negative infectious workup, the patient was diagnosed with CEP secondary to ustekinumab and the drug was stopped. She was started on high dose prednisone and after a prolonged taper over 5 months, her symptoms and nodules and reticulations on her CT scan resolved. DISCUSSION: This case exemplifies the importance of identifying drug-induced lung diseases which in many cases might not have a strong temporal association with the symptom onset. It also highlights that some drugs owing to their long elimination half-time can remain in the system for a prolonged period and continues to cause symptoms despite their cessation and require prolonged treatment and reassurance. CONCLUSION: The association of eosinophilic pneumonia with ustekinumab, a drug used in the treatment of psoriasis and other autoimmune diseases, is rare and there is a paucity of literature regarding this association.

A rare case of refractory asthma managed with azathioprine.

Introduction: Azathioprine is an immune-modulating agent used in the management of autoimmune diseases and in preventing graft rejection. Its role in the management of refractory asthma is not very well-established.Case study: A 47-year-old female with an underlying severe refractory asthma, managed with high dose steroids, was seen as an outpatient. Her course was complicated by frequent asthma exacerbation and severe adverse effects of chronic steroid use. Her symptoms did not respond to standard asthma management per Guidelines for the Diagnosis and Management of Asthma 1. She was tried on other management which included methotrexate and omalizumab injections without success. Azathioprine was started as a steroid-sparing agent following which her symptoms showed dramatic improvement with fewer exacerbations, higher peak flow measurements, and she was able to wean down her daily prednisone dose from 60 mg/day to 5 mg/day.Conclusion: Azathioprine is still an investigational agent for the management of asthma and more research needs to be done to evaluate its role. To our knowledge, this is the second case report which details the therapeutic role of Azathioprine in the management of asthma.