Pulmonary hypertension in eosinophilic versus noneosinophilic COPD.

BACKGROUND: The eosinophilic COPD phenotype is associated with greater airway remodelling, exacerbation risk and steroid responsiveness. However, little is known about the prevalence and characteristics of pulmonary hypertension (PH) in this patient population. METHODS: We retrospectively evaluated a cohort of COPD patients with right heart catheterisation (RHC) data at a university hospital between January 2011 and May 2019 and compared the pulmonary vascular profile and prevalence of PH between eosinophilic and noneosinophilic patients using a definition of eosinophilic COPD as at least three blood eosinophil values ≥300 cells·µL-1. We used multivariable logistic regression analyses to examine the association between eosinophilic COPD and various PH categories adjusting for age, sex, body mass index, forced expiratory volume in 1 s (%), smoking status and use of supplemental oxygen. RESULTS: Among 106 COPD patients with RHC data and at least three blood eosinophil values, 25% met the definition of eosinophilic COPD. Fewer patients among the eosinophilic group required long-term oxygen therapy (69% versus 93%, p=0.001) and total lung capacity was significantly lower in the eosinophilic group (p=0.006). This group had higher mean pulmonary arterial pressure (mPAP) (median (interquartile range) 30 (27-41) mmHg versus 25 (22-30) mmHg, p=0.001) and pulmonary vascular resistance (PVR) (4 (2.8-5.1) Wood units versus 2.9 (2.1-4.1) Wood units, p=0.018). On multivariable logistic regression analyses, eosinophilic phenotype was associated with PH (adjusted (a)OR 6.5, 95% CI 1.4-30.7; p=0.018) and pre-capillary PH (aOR 3.2, 95% CI 1.1-9; p=0.027), but not severe PH (aOR 2.1, 95% CI 0.6-7.2; p=0.219). CONCLUSION: Eosinophilic COPD was associated with higher mPAP and PVR and increased likelihood of PH. More studies are needed to further explore this finding.

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.

Pulmonary Embolism in Acute Asthma Exacerbation: Clinical Characteristics, Prediction Model and Hospital Outcomes.

PURPOSE: Little is known about the characteristics and impact of acute pulmonary embolism (PE) during episodes of asthma exacerbation. We aimed to characterize patients diagnosed with acute PE in the setting of asthma exacerbation, develop a prediction model to help identify future patients and assess the impact of acute PE on hospital outcomes. METHODS: We included 758 patients who were treated for asthma exacerbation and underwent a computed tomographic pulmonary angiography (CTA) during the same encounter at a university-based hospital between June 2011 and October 2018. We compared clinical characteristics of patients with and without acute PE and developed a machine learning prediction model to classify the PE status based on the clinical variables. We used multivariable regression analysis to evaluate the impact of acute PE on hospital outcomes. RESULTS: Twenty percent of the asthma exacerbation patients who underwent CTA had an acute PE. Factors associated with acute PE included previous history of PE, high CHA2DS2-VASc score, hyperlipidemia, history of deep vein thrombosis, malignancy, chronic systemic corticosteroids use, high body mass index and atrial fibrillation. Using these factors, we developed a random forest machine learning prediction model which had an 88% accuracy in classifying the acute PE status of the patients (area under the receiver operating characteristic curve = 0.899; 95% confidence interval: 0.885-0.913). Acute PE in asthma exacerbation was associated with longer hospital stay and intensive care unit stay. CONCLUSION: It is important to consider acute PE, a potentially life-threatening event, in the setting of asthma exacerbation especially when other risk factors are present.

Patient With Slow-Growing Mediastinal Mass Presents With Chest Pain and Dyspnea.

A 52-year-old white woman presented with severe pain over the right upper abdomen and nonpleuritic, right-sided, lower chest-wall pain. Her pain had progressively gotten more frequent and severe over the last 5 months. It was also associated with a nonexertional, pressure-like sensation in the central chest. The patient denied any shortness of breath, fevers, cough, or any sputum production. She was taking levothyroxine for hypothyroidism and was a 30-pack-year current smoker; there was no history of drug abuse or occupational exposure. Previous chest radiographs dating back to 5 years consistently showed an elevated right-sided hemidiaphragm without any infiltrates or effusions; cardiomediastinal structures were unremarkable. She had not had a previous workup for these abnormal findings.

Novel therapies in asthma: leukotriene antagonists, biologic agents, and beyond.

Asthma is one of the most common conditions seen in clinical practice and carries both a significant disease burden in terms of patient morbidity and a high economic burden in both direct and indirect costs. Despite this, it remains a comparatively poorly understood disease, with only modest advances in treatment over the past decade. Corticosteroids remain the cornerstone of therapy. Both patient compliance with medications and physician adherence to evidence-based guidelines are often poor, and a high percentage of patients continue to have inadequately controlled disease even with optimal therapy. Following a contextual overview of the current treatment guidelines, this review focuses on novel asthma therapies, beginning with the introduction of the leukotriene receptor antagonist zafirlukast in the 1990s, continuing through advanced endoscopic therapy and into cytokine-directed biologic agents currently in development. Along with clinically relevant biochemistry and pharmacology, the evidence supporting the place of these therapies in current guidelines will be highlighted along with data comparing these agents with more conventional treatment. A brief discussion of other drugs, such as those developed for unrelated conditions and subsequently examined as potential asthma therapies, is included.

Pulmonary arterial hypertension: classification and therapy with a focus on prostaglandin analogs.

Pulmonary arterial hypertension, part of the larger spectrum of disorders causing pulmonary hypertension, is a complex and progressive disease of multiple etiologies that ultimately leads to vascular remodeling, right-sided heart failure, and death. Advances in treatment over the past 15 to 20 years have dramatically reduced the morbidity and mortality of the disease, but often have significant drawbacks. Of the more recently approved therapies, the prostaglandin analogs have been shown to have the greatest therapeutic benefit but are also the most difficult to administer, many being given as continuous intravenous infusions in the ambulatory setting. After a case presentation highlighting some of the challenges that accompany treatment with these agents, this article reviews the diagnosis and classification of pulmonary hypertension and pulmonary arterial hypertension and gives a brief overview of the various other pharmacologic agents used in its treatment. A more comprehensive review of the biochemistry of prostaglandins and the pharmacology and clinical use of this class of drugs follows. Recommended treatment guidelines are also discussed.