key: cord-0797471-kwq5h3x4 authors: Channick, Colleen L.; Garrison, Garth; Huie, Tristan J.; Narewski, Erin; Caplan-Shaw, Caralee; Cho, Josalyn; Rafeq, Samaan; Alalawi, Raed; Alashram, Rami; Bailey, Kristina L.; Carmona, Eva M.; Habib, Naomi; Kapolka, Rebecca; Krishnan, Amita; Lammi, Matthew R.; Peck, Tyler; Pennington, Kelly M.; Rali, Parth; Small, Bronwyn L.; Swenson, Colin; Witkin, Alison; Hayes, Margaret M. title: ATS Core Curriculum 2020. Adult Pulmonary Medicine date: 2020-10-08 journal: ATS scholar DOI: 10.34197/ats-scholar.2020-0016re sha: c06583736128fd372e98f5b57983e389e25a5eb9 doc_id: 797471 cord_uid: kwq5h3x4 The American Thoracic Society Core Curriculum updates clinicians annually in adult and pediatric pulmonary disease, medical critical care, and sleep medicine in a 3- to 4-year recurring cycle of topics. The topics of the 2020 Pulmonary Core Curriculum include pulmonary vascular disease (submassive pulmonary embolism, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension) and pulmonary infections (community-acquired pneumonia, pulmonary nontuberculous mycobacteria, opportunistic infections in immunocompromised hosts, and coronavirus disease [COVID-19]). · Risk stratification and treatment (particularly reperfusion therapies) for submassive pulmonary embolism involve a complex decision-making process that can be best accomplished with involvement of a multidisciplinary pulmonary embolism response team. · Echocardiography is the recommended screening test for pulmonary hypertension. To confirm a diagnosis of pulmonary hypertension, right heart catheterization is required, with guidelines now recommending a mean pulmonary arterial pressure cutoff of >20 mm Hg to make a diagnosis of pulmonary hypertension. · The treatments available for chronic thromboembolic pulmonary hypertension have expanded to include medical, surgical, and percutaneous options. Thus, selection of the most appropriate treatment strategy requires multidisciplinary assessment by a center with chronic thromboembolic pulmonary hypertension expertise. · Recent updates in the guidelines for diagnosis and treatment of community-acquired pneumonia have downplayed the role of sputum cultures and procalcitonin in nonsevere community-acquired pneumonia. · The nodular-bronchiectatic phenotype of nontuberculous mycobacterial pulmonary disease is commonly seen in tall, thin postmenopausal women without significant smoking history, and the fibrocavitary phenotype predominantly affects elderly male smokers with underlying tobaccorelated lung disease. Treatment of Mycobacterium avium complex pulmonary disease should be continued for 12 months beyond negative culture conversion. · Opportunistic infections in the immunocompromised host carry high morbidity and mortality. Culture confirmation and histopathologic confirmation are often the gold-standard diagnostics tools but lack sensitivity. Laboratory tests (polymerase chain reaction [PCR] assays, antigen testing, and serology) in conjunction with compatible clinical and radiologic findings are alternative tools that can rapidly and accurately aid in the diagnosis. · The test currently recommended for the diagnosis of coronavirus disease (COVID- 19) is the nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR. Treatment focuses on supportive care, with close monitoring for rapidly increasing oxygen demands and impending respiratory failure. Although there are no randomized controlled trials of ventilator management of severe COVID-19, use of strategies beneficial in other causes of acute respiratory distress syndrome is recommended. COVID-19-specific therapies are under intense investigation with preliminary data emerging. Pulmonary embolism is the third most common cause of death in hospitalized patients, with a presentation that ranges from no symptoms to sudden death (1) . In the absence of hypotension, pulmonary embolism with objective evidence of right ventricular dysfunction noted on computed tomographic (CT) pulmonary angiography (CTPA) or transthoracic echocardiography and/or because of cardiac biomarker elevation (BNP [brain natriuretic peptide], NT-proBNP [N-terminal pro-BNP], or troponin) is termed submassive with right ventricular strain by the American Heart Association or intermediate risk by the European Society of Cardiology (2, 3) . In addition, the European Society of Cardiology incorporates the Pulmonary Embolism Severity Index (PESI) or the simplified PESI, validated prognostic scores, into pulmonary embolism classification and further subclassifies intermediate-risk pulmonary embolism into two categories: intermediate-low risk and intermediate-high risk (2) ( Table 1 ). The clinical course of submassive pulmonary embolism is highly variable. A subset of patients will progress to high-risk (massive) pulmonary embolism (pulmonary embolism with hypotension) (2, 3 ). An elevated PESI or simplified PESI score, severe pulmonary embolismrelated functional impairment, and signs of reduced end-organ perfusion (e.g., increased lactate or renal impairment) are associated with an increased risk of hemodynamic deterioration (1). The primary focus of submassive pulmonary embolism management is prompt and effective anticoagulation, unless contraindicated (1, 4) . Advanced therapies, including systemic thrombolysis and catheter-based treatments (catheter-directed thrombolysis and catheterbased embolectomy), are available to treat selected patients with submassive pulmonary embolism (1, 4) . These therapies have been shown to reduce clot burden, improve hemodynamics, and improve right ventricular function in the short term. However, their ability to impact short-and long-term mortality, long-term symptoms, and functional status has not been clearly established (1) . Advanced therapies are not without risk, as bleeding and procedure-related complications can be fatal (1, 4) . Quantifying these risks is critical during decision-making and can be achieved by using available bleeding-risk scores such as the El Registro Informatizado de Pacientes con Enfermedad TrombóEmbolica score, which assesses the risk of major bleeding during (2) . More recently, there has been increased recognition that CTEPH represents the most severe end of the spectrum of chronic pulmonary embolism. Patients with pulmonary embolism can also develop chronic thromboembolic disease (CTED), involving similar pathophysiology and symptoms without resting pulmonary hypertension. These patients may report exercise limitation owing to either exercise-induced pulmonary hypertension or increased dead-space ventilation. Dyspnea and exercise intolerance are common in both CTEPH and CTED, although symptoms are nonspecific and may be mistaken for those of other diseases (3) . As many patients with diagnosed CTEPH have not previously received a diagnosis of acute pulmonary embolism or deep vein thrombosis (DVT), it is important to maintain a high degree of clinical suspicion. Risk factors for the development of CTEPH include antiphospholipid antibody syndrome, chronic inflammatory states, splenectomy, and prior pulmonary embolism (4). All patients with diagnosed pulmonary hypertension should receive screening for CTEPH, as it is the only form of pulmonary hypertension that is potentially curable without lung transplantation. The ventilation-perfusion ( _ V/ _ Q ) lung scan is the preferred screening test. Although CTPA often shows signs of CTEPH, it is less sensitive than a _ V/ _ Q scan in detecting the vascular filling defects associated with CTEPH (Video 1) (5). Right-heart catheterization (RHC) is required to quantify the presence and severity of pulmonary hypertension. Pulmonary angiography is performed to define the location and severity of pulmonary vascular obstruction, an important step in assessing treatment options. For patients with CTED, exercise testing may be useful to help quantify the degree of disease and to evaluate for a pulmonary vascular cause of exercise limitation. Pulmonary thromboendarterectomy (PTE) is first-line therapy for patients with surgically accessible disease. Although invasive, PTE offers an opportunity for cure. Survival and functional status are markedly improved in appropriately selected patients (6) . For patients who are not surgical candidates, either owing to comorbidities or disease location, or for those who have residual disease despite PTE, balloon pulmonary angioplasty and pharmacologic therapy are available alternatives. Balloon pulmonary angioplasty is a staged procedure and has been associated with improvements in both hemodynamics and symptoms as measured by functional class (7). Riociguat, a soluble guanylate cyclase stimulator, is currently the only U.S. Food and Drug Administration (FDA)approved medical therapy for residual or inoperable CTEPH. All patients should be treated with indefinite anticoagulation. As CTEPH is a rare disease with complex and invasive treatment options, it is essential that patients be evaluated at a specialized CTEPH center that can Video 1. This video shows the complementary use of ventilation-perfusion ( _ V/ _ Q) scan and pulmonary angiography in the diagnosis and treatment of chronic thromboembolic pulmonary hypertension. The _ V/ _ Q scan shows absent perfusion to the bilateral lower lobes. A right-heart catheterization and pulmonary angiogram is then performed (only the right side is shown), confirming complete occlusion of the descending pulmonary artery with pulmonary hypertension. The patient underwent successful pulmonary thromboendarterectomy, and the surgical specimen is shown. provide multidisciplinary care (8) . In such a setting, pulmonologists with expertise in pulmonary hypertension, interventional specialists (typically cardiologists or radiologists), and surgeons can review individual cases to determine the best course of treatment. At the 2018 sixth World Symposium on Pulmonary Hypertension, major revisions were made to the definition of pulmonary hypertension from a mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg to a new definition of >20 mm Hg. A PVR cutoff of 3 WU was also recommended to discriminate elevation of mPAP owing to precapillary pulmonary vascular disease from other causes, such as high cardiac output or elevations in pulmonary artery wedge pressure (PAWP) (1, 2). Pulmonary hypertension is grouped into five clinical classifications on the basis of pathophysiologic mechanisms, clinical presentation, hemodynamic characteristics, and treatment. The two main modifications to group 1 pulmonary arterial hypertension (PAH) were the inclusion of the subgroups "PAH with overt features of venous/capillary involvement" and "PAH long-term responders to calcium channel blockers (CCBs)." In addition, methamphetamines and dasatinib were added as drugs that definitely cause drug-induced PAH (2) . Echocardiography is the most important screening tool in patients suspected of having pulmonary hypertension on the basis of history, symptoms, physical examination findings, and biomarkers (Video 2). RHC remains the gold standard for establishing the diagnosis of pulmonary hypertension. _ V/ _ Q scanning should be performed in all patients to screen for CTEPH. Patients with scleroderma, the human immunodeficiency virus (HIV), and portal hypertension have elevated risk for developing pulmonary hypertension and require more aggressive screening (3). Patients with idiopathic, heritable, and drug-or toxin-associated PAH should undergo acute vasoreactivity testing during RHC to predict responsiveness to CCBs. If used, adequate response should be confirmed by sustained hemodynamic improvement after 1 year of treatment. A multiparametric risk-stratification approach is recommended to assess the severity and prognosis of PAH patients and to guide treatment, both at time of diagnosis and on follow-up. With rare exception, patients who are at low/intermediate risk should initially be treated with oral combination therapy. In high-risk patients, initial combination therapy including intravenous prostacyclin analogs is recommended. If the treatment approach results in a low-risk status within 3-6 months, the regimen should be continued. If the patient is still in intermediate-or high-risk status, escalation of therapy is recommended (4). Pulmonary hypertension is a common complication of left-heart disease (LHD) owing to an increase in left-sided filling pressures. The hemodynamic definition of pulmonary hypertension-LHD is as follows: 1) isolated postcapillary pulmonary hypertension (PAWP > 15 mm Hg; mPAP > 20 mm Hg; PVR < 3 WU) and 2) combined pre-and postcapillary pulmonary hypertension (PAWP > 15 mm Hg; mPAP > 20 mm Hg; PVR ≥ 3 WU]). Distinguishing between PAH and pulmonary hypertension-LHD may be difficult; therefore, determining pretest probability and evaluating hemodynamics is vital for the confirmation of any PAH diagnosis. Evidence-based guidelines recommend against using PAH-specific drugs in the treatment of pulmonary hypertension-LHD (1, 5) . Chronic lung disease is frequently complicated by pulmonary hypertension, resulting in reduced functional status and worse outcomes (6) . RHC should be performed only when significant pulmonary hypertension is suspected and management (1). Several important updates are summarized in Table 2 . The diagnosis of CAP is based on patient history, physical examination, and chest imaging. Previously, a distinction was made between pneumonia acquired as an outpatient and pneumonia acquired as an inpatient (health care-associated pneumonia) to guide evaluation and therapy. (5) . Procalcitonin testing is occasionally used to determine whether CAP is bacterial or viral in origin. However, an appropriate threshold for procalcitonin in bacterial pneumonia has not been determined. Therefore, use of procalcitonin as the sole metric for withholding antibiotic treatment is not recommended, and adults with clinical and radiologic features of CAP should receive appropriate initial antibiotic treatment even when procalcitonin is low (1). The recommendations for initial antibiotic coverage have shifted slightly in the new guidelines (1). Healthy outpatients can be treated with amoxicillin, doxycycline, or a macrolide when pneumococcal resistance is low (<25%). Outpatients with comorbidities, including heart, lung, or renal disease, should receive amoxicillin/clavulanate or a cephalosporin and a macrolide or monotherapy with a respiratory fluoroquinolone. with severe pneumonia, a β-lactam plus a macrolide or a β-lactam plus a respiratory fluoroquinolone may be initiated with additional coverage for MRSA or P. aeruginosa if there is previous infection with or risk factors for these organisms. In the 2019 ATS/IDSA CAP guideline, the routine use of corticosteroids is not recommended; however, it may be considered in patients with refractory septic shock (1). New guidelines for CAP recommend shifting our focus toward which pathogens to target in therapy, and the guidelines delineate treatment and investigational recommendations primarily on the basis of severe and nonsevere CAP. Nontuberculous mycobacteria (NTM) are a group of ubiquitous environmental organisms found mainly in water and soil. Of the over 200 known species of NTM, only a fraction are considered human pathogens (1). Human exposure may occur through the municipal water supply, recreational water activities, and gardening (1). NTM are opportunistic pathogens with variable mechanisms of pathogenicity. The most common clinical manifestations of NTM-PD are cough, fatigue, malaise, dyspnea, weight loss, subjective fever, and sputum production that may be accompanied by hemoptysis (4) . There are two primary disease phenotypes in NTM-PD. The nodular-bronchiectatic phenotype is commonly seen in tall, thin, postmenopausal women without significant smoking history, although nonsmoking males increasingly compose part of this disease cohort. Radiographically, the phenotype is characterized by centrilobular pulmonary nodules, tree-inbud opacities, and/or cylindrical bronchiectasis, often within the same lobe (4) (Figure 1 ). The fibrocavitary disease phenotype is more commonly seen in older male smokers with underlying chronic lung disease, most commonly emphysema. Chest imaging typically shows an upperlobe thick-walled cavitary lesion, which may have an appearance similar to that of active pulmonary tuberculosis ( Figure 2 consideration of a thrice-weekly intravenous aminoglycoside, is recommended. It is important to avoid macrolide monotherapy, as this therapy may promote macrolide resistance (6) . Sputum acid-fast bacillus cultures should be monitored every 1-3 months while on treatment, and therapy is continued for 12 months after sputum culture conversion (7). (Table 3) . Aspergillus species cause disease in hosts with impaired cellular immunity, neutrophil dysfunction, or structural lung disease. Invasive pulmonary aspergillosis is the most severe manifestation and presents as fever, cough, pleuritic chest pain, hemoptysis, and nonspecific nodular or ground-glass infiltrates on chest imaging (Figures 3 and 4) . Hosts with prolonged neutropenia, those receiving prolonged highdose systemic corticosteroids, and those after solid-organ transplant or bone marrow transplant are at greatest risk (3). Diagnosis requires direct visualization of Aspergillus species invading tissue or blood vessels on histopathologic examination. As biopsies can be difficult to obtain because of illness severity, antigen testing (galactomannan cellwall component) and Aspergillus polymerase chain reaction (PCR) measured on either serum or bronchoalveolar lavage (BAL) may be a less invasive approach to aid diagnosis (4). C. neoformans causes disease in hosts with severe defects in cellular immunity. Hosts with exposure to pigeons or other bird droppings may be at higher risk. C. neoformans enters the host via inhalation and has a predilection for the central nervous system. Patients present with fever, cough, and headache or meningeal signs. Chest imaging may show pulmonary nodules, lymphadenopathy, and/or pleural effusions ( Figure 5 ). Culture or direct visualization is the gold standard for diagnosis, but antigen testing of serum or cerebrospinal fluid is often used, and thus lumbar puncture is recommended during evaluation (5). P. jirovecii pneumonia (PJP) typically occurs in patients with defects in cell-mediated immunity, but reports of PJP in patients receiving rituximab exist (6) . Presentation ranges from mild nonproductive cough to severe hypoxemic respiratory failure with diffuse infiltrates on chest imaging ( Figure 6 ). Because P. jirovecii cannot be cultured, direct visualization of the organism on histopathologic specimens is the gold standard for diagnosis. The diagnosis is often made using PCR testing on BAL specimens (7) . Serum β-1,3-D-glucan may also be significantly elevated in PJP but is a nonspecific marker of disease. The gold standard for diagnosing most opportunistic infections is direct visualization and/or culture, but this is usually not feasible secondary to illness severity, bleeding risk, and time to culture positivity. Limitations exist with antigen and PCR testing modalities. For example, galactomannan may be falsely positive in patients with mucositis (4, 8) and falsely negative in patients on antifungal prophylaxis (3). Serum β-1,3-D-glucan is nonspecific and can be falsely positive in patients receiving hemodialysis, intravenous immunoglobulin, cardiopulmonary bypass, or blood transfusion (9) . PCR testing is limited by contamination and inability to distinguish colonization from infection. Serum Aspergillus PCR has high sensitivity and low specificity with single-sample testing, but sensitivity decreases and specificity increases with repeated samples (3). (9) . Serologic tests are commercially available, but they have variable sensitivity, particularly early in the course of disease. Antibody production is reported to start 1 week after the onset of infection (8) . Characteristic imaging findings at chest radiography include consolidation or ground-glass opacities that are usually bilateral, peripheral, and lower-lobe predominant (10) . Chest CT images often show peripheral, bilateral ground-glass opacities in early or mild disease, whereas cases with severe disease demonstrate more diffuse ground-glass opacities and consolidation; often with reticular abnormality and traction bronchiectasis reflecting more severe lung injury (11) (Figures 7 and 8) . Lung ultrasound shows thickening and irregularity of the pleural line, B-lines, and consolidation, with pleural effusions being uncommon (12) . Laboratory findings are nonspecific and often show an elevation in inflammatory markers (C-reactive protein, erythrocyte sedimentation rate, ferritin), leukopenia, and elevated D-dimer, lactate dehydrogenase, and interleukin-6 levels (13). Risk factors for severe COVID-19 infection include advanced age; chronic medical conditions such as advanced cardiopulmonary disease, hypertension, diabetes, and obesity; cancer; and immunosuppression (14) . African American, Native American, and Hispanic persons are much more likely to be hospitalized than non-Hispanic white persons (14) . Mortality rates have varied (1.4-3.2%), with a larger series of 44,672 confirmed cases reporting a case fatality rate of 2.3% (1, 5) . Reports of mortality among critically ill patients have ranged from 16.7% to >40% (15) (16) (17) . Renal failure requiring renal replacement therapy and mechanical ventilation are risk factors associated with a higher mortality (16, 17) . Scarcity of resources to provide advanced respiratory and renal support may have contributed to increased mortality rates in locations where the caseload has exceeded capacity. Treatment focuses on supportive care, with close monitoring for rapidly increasing oxygen demands and impending respiratory failure. Intubated patients should receive best practices for acute respiratory distress syndrome, including lung-protective ventilation strategies, prone positioning, and conservative fluid management (18) (19) (20) . There are currently no FDA-approved therapies for COVID-19, but multiple agents are under investigation. Initial enthusiasm for hydroxychloroquine based on in vitro benefit has waned, as trials have failed to demonstrate a clear benefit for hospitalized patients while highlighting potential, harms including QT interval prolongation and arrhythmias (18, 21, 22) . The antiviral drug remdesivir was shown in a preliminary report to reduce time to recovery in patients who need supplemental oxygen or mechanical ventilation (23) . Treatment with convalescent plasma appears safe, but rigorous studies have not yet demonstrated a benefit (24, 25) . These studies evaluated the clinical response as well as the anti-SARS-CoV-2 antibody levels. A number of antiinflammatory approaches are under investigation, including the interleukin-6 inhibitors tocilizumab and sarilumab. A retrospective study suggested a reduction in the need for mechanical ventilation or death with tocilizumab use (26) . Prospective studies are underway. Preliminary data from the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial (a large multicenter, randomized, open-label study) suggest a 17% reduction in 28-day mortality for hospitalized patients with low-dose dexamethasone (29.0% vs. 40.7%) (27) . The benefit appeared to be greatest in patients with severe disease, whereas no benefit was observed in patients not requiring supplemental oxygen. These data have not yet been published in a peerreviewed journal; however, the observed benefit led the National Institutes of Health COVID-19 Treatment Guidelines Panel to recommend dexamethasone 6 mg daily for up to 10 days for patients receiving mechanical ventilation (18) . Patients with COVID-19 appear to have an increased incidence of thromboembolic events (28) . Although hospitalized patients frequently have coagulation parameters measured, it is unclear how results should influence therapy (18) . Hospitalized patients should receive DVT prophylaxis on the basis of risk stratification independent of COVID-19 status. Those with confirmed or suspected thromboembolic events should receive full-dose anticoagulation (18) . Multiple trials evaluating anticoagulation regimens and thrombolytic use are underway. Multiple COVID-19 vaccines are in development. It is important to recall that data before the pandemic demonstrate that viruses result in 25-44% of all cases of CAP and that 16-49% of pneumonias lead to severe respiratory illness (29, 30) . Coinfections with COVID-19 and other respiratory viruses appear relatively uncommon; however, a case series demonstrated that 20% of samples from patients with COVID-19 infection had other respiratory pathogens identified (6, 31) . A case series describes four patients who presented with COVID-19 and influenza (32) . Diagnostic testing should assess for influenza depending on community activity, as antiviral therapy is indicated for hospitalized patients with influenza (33) . A positive test result for other respiratory viruses does not exclude a diagnosis of COVID-19. Public health efforts aimed at controlling the spread of COVID-19 include social distancing with an emphasis on hand washing and wearing masks in public where social distancing is not possible (particularly indoors). Testing programs and contact tracing are additional public health measures employed to control the spread of disease. 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