A 49-year-old man with ischemic cardiomyopathy and persistent hemoptysis for eighteen months.

Idiopathic pulmonary hemosiderosis (IPH) is a rare cause of recurrent episodes of diffuse alveolar hemorrhage (DAH). IPH commonly manifests with hemoptysis, radiologic chest infiltrates and anemia. The etiology of IPH is unknown, but an immunologic mechanism is widely speculated. The definitive diagnosis of IPH requires a thorough exclusion of other causes of DAH, such as infections, inflammation, malignancy, cardiac diseases, drug and toxin exposure, and medications. Due to the rarity of the disease, a diagnosis is often delayed by years. We present the case of a 49-year-old man with ischemic cardiomyopathy who presented with hemoptysis for eighteen months. Serologic workup was negative for vasculitides and autoimmune diseases. Bronchoscopy revealed DAH. A surgical lung biopsy showed 'bland pulmonary hemorrhage.' A right heart catheterization ruled out cardiac causes of DAH. The patient was diagnosed with IPH and started on systemic corticosteroids with rapid improvement of hemoptysis.

An unusual case of explosive pleuritis without mediastinal shift.

Explosive pleuritis (EP) is an under-reported condition. Although there is no agreed-upon definition, generally, the term EP denotes a dramatic clinical and radiologic progression of pleural space inflammation in the setting of pneumonia. The pleural space inflammation leads to the formation of loculated complex pleural effusion or empyema, and pleural adhesion within a matter of hours, typically in less than 24 hours. Radiologically, these changes are manifested as opacification of the hemithorax with or without contralateral mediastinal shift. Streptococcal pneumonia is the most common cause of EP. Here we present a case and discuss the clinical, microbiologic, radiologic, and treatment aspects of EP. We also scrutinize the medical literature to compare the previously reported cases.

Proposed Pathogenesis of Diffuse Alveolar Hemorrhage in Idiopathic Pulmonary Hemosiderosis.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease that causes diffuse alveolar hemorrhage (DAH). The latest data suggests an immunologic origin of IPH, and a new name, immune mediated pulmonary hemosiderosis (ImPH), has been proposed. However, the exact immunologic mechanism has remained elusive for nearly eight decades despite extensive research, including detailed histopathologic analysis. Although several hypotheses have been proposed to describe the pathobiology of IPH, none of them explain the clinical and histopathologic findings conclusively. In this manuscript, we have presented a new hypothesis for the pathogenesis of DAH in IPH. We hypothesize that DAH in IPH is not immunocomplex mediated but due to histamine, eosinophilic cationic protein (ECP), and possibly vascular endothelial growth factor (VEGF). These bioactive proteins induce endothelial and alveolar epithelial damage, leading to the peri-capillary and intraalveolar escape of RBCs. The deformability of the RBC likely also plays a role. The supranormal secretion of histamine, ECP and VEGF occurs in genetically predisposed individuals with an aberrant immunologic response. The histamine is released from the basophils and possibly the mast cells in response to cytokines secreted by activated lymphocytes. The lymphocyte activation occurs after exposure to a known (gluten) or unknown antigen. The same lymphocyte-derived cytokines also induce eosinophilic degranulation of ECP and VEGF in the pulmonary circulation. We believe that our hypothesis unifies the observed clinical variabilities and histopathologic findings in IPH, and we hope that would promote future research in the field of IPH.

Lipoid Pneumonia.

Lipoid pneumonia occurs due to the accumulation of lipids within the lung tissue. Autopsy series have reported an incidence of 1.0-2.5% in adult and 8.8% in children. Lipoid pneumonia can be from an exogeneous or an endogenous source. Exogenous lipoid pneumonia is often associated with aspiration of fatty materials, whereas endogenous lipoid pneumonia is associated with an accumulation of lipid-rich debris from destroyed alveolar cells. We describe a 75-year-old man who presented with spiculated lung nodules found incidentally on abdominal CT. Reviews of systems were positive for weight loss, and a history of constipation. A PET/CT revealed spiculated nodules with positive fluorodeoxyglucose (FDG) uptakes. A wedge resection was performed with histopathologic findings consistent with exogenous lipoid pneumonia with granulomatous reaction. We report clinical, radiological, and pathological features of exogenous lipoid pneumonia secondary to chronic aspiration mimicking invasive adenocarcinoma. A high index of suspicion for exogenous lipoid pneumonia should be maintained, especially when evaluating patients with abnormal chest radiographic findings and risk factors for aspirations.

Incidental Lung Cavity in the Heartland.

Necrotizing sarcoid granulomatosis (NSG) is a rare inflammatory disease. Although considered by some to be a subtype of sarcoidosis, this opinion is not universal. NSG is histologically characterized by the presence of necrotizing sarcoid like granuloma and granulomatous vasculitis. The exclusion of potential etiologies for necrotizing granulomatous inflammation is necessary to establish a diagnosis of NSG. A 70-year old female presented to our office after she was incidentally found to have a right lung cavitary lesion on a shoulder X-ray. She had an extensive serologic workup for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, mycobacterial and fungal etiologies, but they were all negative. She subsequently underwent bronchoscopic evaluation and biopsies. The histopathologic analysis revealed sarcoid-like granulomatous inflammation with large necrosis and mild granulomatous vasculitis. The pulmonary function test revealed a restrictive ventilatory defect. The patient was treated with steroid therapy with rapid radiologic and spirometric improvement.

Incidence and risk factors for secondary pulmonary infections in patients hospitalized with coronavirus disease 2019 pneumonia.

BACKGROUND: Secondary pulmonary infections (SPI) have not been well described in COVID-19 patients. Our study aims to examine the incidence and risk factors of SPI in hospitalized COVID-19 patients with pneumonia. METHODS: This was a retrospective, single-center study of adult COVID-19 patients with radiographic evidence of pneumonia admitted to a regional tertiary care hospital. SPI was defined as microorganisms identified on the respiratory tract with or without concurrent positive blood culture results for the same microorganism obtained at least 48 h after admission. RESULTS: Thirteen out of 244 (5%) had developed SPI during hospitalization. The median of the nadir lymphocyte count during hospitalization was significantly lower in patients with SPI as compared to those without SPI [0.4 K/uL (IQR 0.3-0.5) versus 0.6 K/uL (IQR 0.3-0.9)]. Patients with lower nadir lymphocyte had an increased risk of developing SPI with odds ratio (OR) of 1.21 (95% CI: 1.00 to 1.47, p = 0.04) per 0.1 K/uL decrement in nadir lymphocyte. The baseline median inflammatory markers of CRP [166.4 mg/L vs. 100.0 mg/L, p = 0.01] and d-dimer (18.5 mg/L vs. 1.4 mg/L, p<0.01), and peak procalcitonin (1.4 ng/mL vs. 0.3 ng/mL, p<0.01) and CRP (273.5 mg/L vs. 153.7 mg/L, p<0.01) during hospitalization were significantly higher in SPI group. CONCLUSIONS: The incidence of SPI in hospitalized COVID-19 patients was 5%. Lower nadir median lymphocyte count during hospitalization was associated with an increased OR of developing SPI. The CRP and d-dimer levels on admission, and peak procalcitonin and CRP levels during hospitalization were higher in patients with SPI.

Indications, Clinical Utility, and Safety of Bronchoscopy in COVID-19.

BACKGROUND: Bronchoscopy is an aerosol-generating procedure and routine use for patients with coronavirus disease 2019 (COVID-19) has been discouraged. The purpose of this review was to discuss the indications, clinical utility, and risks associated with bronchoscopy in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. METHODS: A literature search was performed by using appropriate key terms to identify all relevant articles from medical literature databases up to August 1, 2021. RESULTS: Twelve cohorts (9 retrospective and 3 prospective) reported the performance of 2,245 bronchoscopies in 1,345 patients with COVID-19. The majority of the subjects were male. Nearly two thirds of the bronchoscopies (62%) were performed for therapeutic indications; the rest (38%) were for diagnostic purposes. Bronchoalveolar lavage had an overall yield of 33.1% for SARS-CoV-2 in subjects with negative results of real-time polymerase chain reaction on nasopharyngeal specimens. The incidence of a secondary infection ranged from 9.3% to as high as 65%. Antibiotics were changed in a significant number of the subjects (14%-83%) based on the bronchoscopic findings. Bronchoscopy was well tolerated in most subjects except those who required noninvasive ventilation, in whom the intubation rate after the procedure was 60%. The rate of transmission of SARS-CoV-2 among health-care workers was minimum. CONCLUSIONS: Bronchoscopy in patients with COVID-19 results in a significant change in patient management. Transmission of SARS-CoV-2 seems to be low with consistent use of appropriate personal protective equipment by health-care workers. Therefore, bronchoscopic evaluation should be considered for all diagnostic and therapeutic indications in this patient population.

Lung transplant to manage end-stage lung disease due to idiopathic pulmonary hemosiderosis: A review of the literature.

Idiopathic pulmonary hemosiderosis (IPH) is a rare immunological disease with a genetic predisposition. It is characterized by recurrent episodes of diffuse alveolar hemorrhage (DAH). Timely use of immunosuppressive medications has significantly improved overall outcomes, including mortality. Still, uncontrolled and frequent episodes of DAH can eventually cause pulmonary fibrosis, leading to end-stage lung disease (ESLD). The objective of the present project was to scrutinize the literature and summarize the demographic, clinical, radiological, and histopathological features, as well as the overall outcomes, in this patient population following lung transplant. The Medline database was searched using the PubMed platform. Articles published in English between 1960 and 2020 were included in the search. Different search terms were used to identify all patients who underwent lung transplantation to manage ESLD due to IPH. Only four cases of lung transplantation have been reported in the literature in patients with IPH. All but one of these underwent deceased donor lung transplant; recurrence was reported in two of these patients and suspected in the third. One patient received living donor lung transplant and had no recurrence during a five-year follow-up. Patients with IPH should not be excluded from lung transplantation because the disease may not recur in all patients, and even when it does recur it can be promptly treated by increasing immunosuppression.

Differentiation of idiopathic pulmonary hemosiderosis from rheumatologic and autoimmune diseases causing diffuse alveolar hemorrhage: establishing a diagnostic approach.

This narrative review provides an overview of diffuse alveolar hemorrhage (DAH) associated with rheumatologic and autoimmune diseases and their differentiation from idiopathic pulmonary hemosiderosis (IPH). Relevant immunologic diseases associated with DAH are discussed, and a diagnostic flowchart is proposed to establish a "definitive" diagnosis of IPH within the spectrum of DAH. IPH is a rare cause of recurrent DAH both in children and adults. In adults, a definitive diagnosis of IPH requires a lung biopsy and histopathologic examination demonstrating intraalveolar hemorrhage, hemosiderin-laden macrophages, and a variable degree of fibrosis in the absence of both capillaritis and cellular inflammation. The presence of small vessel vasculitis points towards immunologic, well-differentiated, or sometimes undifferentiated rheumatologic diseases. However, it is essential to recognize that many rheumatologic diseases may in the initial phase present with DAH without any evidence of capillaritis, thus mimicking IPH. Although not definitely established, it is likely that immunologic processes are involved in IPH, and we, therefore, suggest the consideration of a more suitable term for the disease, e.g., "Immune-mediated Pulmonary Hemosiderosis" to acknowledge the aberrancy in the immune parameters and a positive response to immunosuppressive therapy.

A 51-Year-Old Man With a Large Posterior Mediastinal Mass.

CASE PRESENTATION: A 51-year-old White male never-smoker presented with intermittent cough and progressive dyspnea. His symptoms started after an exposure to bat guano while cleaning his attic approximately 9 months earlier. He has received several courses of antibiotic and corticosteroid for these symptoms, with short-term relief.

Bronchoscopy During Coronavirus Disease 2019 Pandemic: A Bronchoscopist's Perspective.

Bronchoscopy is a safe and commonly performed procedure for diagnostic as well as therapeutic indications. Bronchoscopy is also an aerosol-generating procedure, and due to the risk of severe acute respiratory syndrome coronavirus 2 transmission during the procedure, routine bronchoscopy has been discouraged by multiple professional societies, despite any solid evidence. There are only a few reports of bronchoscopy in patients with coronavirus disease 2019 in the literature. Bronchoscopy in this patient population plays a crucial role not only in the diagnosis of coronavirus disease 2019 but also in the identification of secondary bacterial or fungal infections and in directing appropriate antimicrobial therapy. Bronchoscopy with therapeutic interventions may be lifesaving. Based on the literature, the risk of coronavirus disease 2019 transmission appears to be low among bronchoscopists and other healthcare workers when appropriate personal protective equipment is used. Bronchoscopy in patients with coronavirus disease 2019 should be strongly considered when clinically indicated.

Pleural abnormalities in COVID-19: a narrative review.

OBJECTIVE: This narrative review aims to provide a detailed overview of pleural abnormalities in patients with coronavirus disease 19 or COVID-19. BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is a novel beta coronavirus responsible for COVID-19. Although pulmonary parenchymal and vascular changes associated with COVID-19 are well established, pleural space abnormalities have not been the primary focus of investigations. METHODS: Narrative overview of the medical literature regarding pleural space abnormalities in COVID-19. The appropriate manuscripts were identified by searching electronic medical databases and by hand searching the bibliography of the identified papers. Pleural abnormalities on transverse and ultrasound imaging are discussed. The incidence, clinical features, pathophysiology, and fluid characteristics of pleural effusion are reviewed. Studies reporting pneumothorax and pneumomediastinum are examined to evaluate for pathogenesis and prognosis. A brief comparative analysis of pleural abnormalities among patients with COVID-19, severe acute respiratory syndrome (SARS), and Middle Eastern respiratory syndrome (MERS) has been provided. CONCLUSIONS: Radiologic pleural abnormalities are common in COVID-19, but the incidence of pleural effusion appears to be low. Pneumothorax is rare and does not independently predispose the patient to worse outcomes. SARS-CoV-2 infects the pleural space; however, whether the pleural fluid can propagate the infection is unclear.

Dyspnea in a 57-Year-Old Man With Recent Viral Illness.

CASE PRESENTATION: A 57-year-old man presented to the ED with a 1-month history of nonproductive cough and shortness of breath. The patient had been in his usual state of health until 2 months before presentation, when he experienced an episode of nonproductive cough and shortness of breath. He was diagnosed clinically with an upper respiratory tract infection; the symptoms resolved after 7 days with conservative therapy alone. One month later, the nonproductive cough and shortness of breath returned. He was treated with a 5-day course of oral azithromycin without any improvement in his symptoms. On presentation to the ED, he denied fever, chills, night sweats, chest pain, arthralgia, myalgia, or hemoptysis. His medical history was significant for hypertension, poorly controlled type 2 diabetes mellitus, and coronary artery bypass grafting. His medications included aspirin, metoprolol, metformin, and glipizide. He denied any history of tobacco, vaping, or recreational drug use. He worked as a cashier in a departmental store and has been doing so for most of his life.

A 75-Year-Old Woman With Pulmonary Nodules and Dyspnea.

CASE PRESENTATION: A 75-year-old woman was referred to the pulmonary office in January 2020 for cough and progressive worsening of shortness of breath over the years. Her medical history was significant for asthma that was diagnosed approximately 10 years earlier, when she first developed dyspnea. A pre-bronchodilator spirometry at that time showed severe airflow obstruction (Fig 1). The patient was incidentally found to have several noncalcified pulmonary nodules on a chest CT scan in 2015, which was obtained as a part of dyspnea workup. She underwent bronchoscopic evaluation with transbronchial biopsy of the largest nodule (1.6 × 1.2 cm) in the right middle lobe. She was diagnosed with low-grade neuroendocrine tumor (typical carcinoid) and had been under surveillance without any progression in the number of nodules or the size of the existing nodules. She was a lifelong nonsmoker and no family history of asthma. Over the years, she received multiple courses of systemic corticosteroids and different inhalers, without any improvement in her symptoms. The patient was frustrated by the lack of perceived benefit, and she discontinued all respiratory medications. She denied any fever, night sweats, exertional chest pain, or seasonal allergies but reported cough, wheezing, and severe exertional shortness of breath. She was unable to walk more than 20 feet at a time. She had no pets at home and did not travel outside the United States. Her only home medications were multivitamins and low-dose aspirin.

Does COVID-19 pneumonia signify secondary organizing pneumonia?: A narrative review comparing the similarities between these two distinct entities.

Multiple observational studies have described the similarities between COVID-19 pneumonia and organizing pneumonia (OP). These two entities clinically manifest with mild and subacute respiratory symptoms, often with a delayed diagnosis due to the atypical ARDS and silent hypoxemia presentation. Radiological features are often indistinguishable between the two. With the increase in antemortem lung biopsies and autopsies being performed, more histopathological findings of OP and its variant, acute fibrinous and organizing pneumonia (AFOP), are being diagnosed. These entities are known complications of viral infections as a delayed immunological process, explaining the favorable response to corticosteroids. Clinicians should be vigilant to diagnose this under-recognized entity of secondary OP in people with COVID-19 when clinical deterioration occurs, especially with compatible radiologic findings and recent cessation of corticosteroids. Despite the proven benefits of corticosteroids in treating COVID-19, treatment approaches can be more effective as OP often requires higher doses and a more prolonged therapy duration for remission and preventing relapses. The purpose of our narrative review is to compare the similarities between COVID-19 pneumonia and OP, emphasizing the clinical, radiological, and histopathological features based on the evidence available in the literature.

The incidence, clinical characteristics, and outcomes of pneumothorax in hospitalized COVID-19 patients: A systematic review.

BACKGROUND: Pneumothorax has been frequently described as a complication of COVID-19 infections. OBJECTIVE: In this systematic review, we describe the incidence, clinical characteristics, and outcomes of COVID-19-related pneumothorax. METHODS: Studies were identified through MEDLINE, Pubmed, and Google Scholar databases using keywords of "COVID-19," "SARS-CoV-2," "pneumothorax," "pneumomediastinum," and "barotrauma" from January 1st, 2020 to January 30th, 2021. RESULTS: Among the nine observational studies, the incidence of pneumothorax is low at 0.3% in hospitalized COVID-19 patients. However, the incidence of pneumothorax increases to 12.8-23.8% in those requiring invasive mechanical ventilation (IMV) with a high mortality rate up to 100%. COVID-19-related pneumothorax tends to be unilateral and right-sided. Age, pre-existing lung diseases, and active smoking status are not shown to be risk factors. The time to pneumothorax diagnosis is around 9.0-19.6 days from admission and 5.4 days after IMV initiation. COVID-19-related pneumothoraces are associated with prolonged hospitalization, increased likelihood of ICU admission and death, especially among the elderly. CONCLUSION: COVID-19-related pneumothorax likely signify greater disease severity. With the high variability of COVID-19-related pneumothorax incidence described, a well-designed study is required to better assess the significance of COVID-19-related pneumothorax.