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As the U.S. health care system changes and technology alters how doctors work and learn, medical schools and their faculty are compelled to modify their curricula and teaching methods. In this article, educational leaders and key faculty describe how the Pathways curriculum was conceived, designed, and implemented at Harvard Medical School. Faculty were committed to the principle that educators should focus on how students learn and their ability to apply what they learn in the evaluation and care of patients. Using the best evidence from the cognitive sciences about adult learning, they made major changes in the pedagogical approach employed in the classroom and clinic. The curriculum was built upon 4 foundational principles: to enhance critical thinking and provide developmentally appropriate content; to ensure both horizontal integration between courses and vertical integration between phases of the curriculum; to engage learners, foster curiosity, and reinforce the importance of student ownership and responsibility for their learning; and to support students' transformation to a professional dedicated to the care of their patients and to their obligations for lifelong, self-directed learning.The practice of medicine is rapidly evolving and will undoubtedly change in multiple ways over the career of a physician. By emphasizing personal responsibility, professionalism, and thinking skills over content transfer, the authors believe this curriculum will prepare students not only for the first day of practice but also for an uncertain future in the biological sciences, health and disease, and the nation's health care system, which they will encounter in the decades to come.

Pulmonary arterial hypertension (PAH) is a subtype of pulmonary hypertension (PH), characterized by pulmonary arterial remodeling. The prevalence of PAH is approximately 10.6 cases per 1 million adults in the US. Untreated, PAH progresses to right heart failure and death.Pulmonary hypertension is defined by a mean pulmonary artery pressure greater than 20 mm Hg and is classified into 5 clinical groups based on etiology, pathophysiology, and treatment. Pulmonary arterial hypertension is 1 of the 5 groups of PH and is hemodynamically defined by right heart catheterization demonstrating a mean pulmonary artery pressure greater than 20 mm Hg, a pulmonary artery wedge pressure of 15 mm Hg or lower, and a pulmonary vascular resistance of 3 Wood units or greater. Pulmonary arterial hypertension is further divided into subgroups based on underlying etiology, consisting of idiopathic PAH, heritable PAH, drug- and toxin-associated PAH, pulmonary veno-occlusive disease, PAH in long-term responders to calcium channel blockers, and persistent PH of the newborn, as well as PAH associated with other medical conditions including connective tissue disease, HIV, and congenital heart disease. Early presenting symptoms are nonspecific and typically consist of dyspnea on exertion and fatigue. Currently approved therapy for PAH consists of drugs that enhance the nitric oxide-cyclic guanosine monophosphate biological pathway (sildenafil, tadalafil, or riociguat), prostacyclin pathway agonists (epoprostenol or treprostinil), and endothelin pathway antagonists (bosentan and ambrisentan). With these PAH-specific therapies, 5-year survival has improved from 34% in 1991 to more than 60% in 2015. Current treatment consists of combination drug therapy that targets more than 1 biological pathway, such as the nitric oxide-cyclic guanosine monophosphate and endothelin pathways (eg, ambrisentan and tadalafil), and has shown demonstrable improvement in morbidity and mortality compared with the previous conventional single-pathway targeted monotherapy.Pulmonary arterial hypertension affects an estimated 10.6 per 1 million adults in the US and, without treatment, typically progresses to right heart failure and death. First-line therapy with drug combinations that target multiple biological pathways are associated with improved survival.

A 74-year-old woman presented with a 6-week history of progressive dyspnea on exertion. Eight weeks before this presentation, she had been traveling in Italy and had been walking up to 4 miles per day. Progressive dyspnea on exertion had developed after she returned to the United States. She also noted a nonproductive cough, fatigue, loss of appetite, and an unintentional weight loss of 9 kg over the previous 6 months. She had no fevers, chills, night sweats, hemoptysis, wheezing, chest pain, palpitations, orthopnea, paroxysmal nocturnal dyspnea, swelling of the legs or feet, abdominal pain, nausea, vomiting, melena, or hematochezia. Four weeks before this presentation, she had presented to an emergency department at another institution, where imaging was performed. Chest radiography showed no pneumonia, and venous ultrasonography of both legs showed no deep venous thrombosis. A 5-day course of prednisone and azithromycin was prescribed; however, her symptoms continued to worsen, and she began to have dyspnea when she was at rest.

A variety of known etiologic agents can cause diffuse parenchymal lung disease, also referred to as interstitial lung disease. These include inorganic dusts (the pneumoconioses), organic antigens (the cause of hypersensitivity pneumonitis), drugs, and radiation to the thorax. The most common of the disorders classified as pneumoconioses include silicosis, coal worker's pneumoconiosis, asbestosis, and berylliosis. Some of these disorders involve toxicity to, or activation of macrophages, whereas beryllium induces a hypersensitivity reaction that clinically mimics sarcoidosis. Many organic antigens can induce a hypersensitivity pneumonitis, which can have a presentation ranging from an acute illness with transient pulmonary infiltrates to a chronic diffuse parenchymal lung disease. A wide range of drugs are now known to be associated with parenchymal lung disease, with the most important categories being cancer chemotherapeutic agents and a variety of newer biological drugs, but a number of other miscellaneous drugs have also been implicated. Finally, radiation therapy directed to the thorax, most commonly for breast cancer, lung cancer, or Hodgkin disease, can be associated with an acute inflammatory process in the lungs (radiation pneumonitis) or a more chronic fibrotic process (radiation fibrosis).

In the process of exchanging thousands of liters of air each day, the lung is exposed to a multitude of microorganisms and foreign substances transported with the inhaled air. To protect itself against potentially toxic inhaled material, the respiratory system has evolved complex protective mechanisms that can be conceptualized as different groups of components. Each appears to have a distinct role, but a tremendous degree of redundancy and interaction exists among different components. This chapter considers how the lung protects itself against the infectious agents to which it is exposed. Although this chapter focuses on protective mechanisms against infection, defenses against non-infectious substances, especially inhaled particulate material, also are addressed. The major categories of defense mechanisms discussed include (1) physical or anatomic factors relating to deposition and clearance of inhaled material, (2) antimicrobial peptides, (3) phagocytic and inflammatory cells that interact with the inhaled material, and (4) adaptive immune responses, which depend on prior exposure to and recognition of the foreign material. The chapter concentrates on the aspects of the host defense system specific to the lung and then proceeds with a discussion of several ways the system breaks down, resulting in an inability to handle microorganisms and an increased risk for certain types of respiratory tract infection. The chapter concludes by briefly considering how we can activate or augment specific immune responses through immunization, thus enhancing defenses against selected respiratory pathogens.

Chapter 29 describes the management of the two broad classes of respiratory failure – hypoxemic respiratory failure and hypercapnic respiratory failure. The goals of each are described in terms of the principles of support and the desired targets for gas exchange. The available types of mechanical ventilation are presented, focusing on pressure support ventilation and pressure-controlled ventilation as the major modes of pressure-limited ventilation, and assist-control ventilation and synchronized intermittent mandatory ventilation as the major modes of volume-cycled ventilation. Positive end-expiratory pressure is explained as a technique to avoid alveolar closure during expiration, increase functional residual capacity, reduce the amount of shunting, and improve oxygenation. When ventilated patients are sufficiently stable, a daily trial of spontaneous breathing is used to assess the patient's ability to be maintained off ventilatory support. The technique of noninvasive ventilation as an alternative to intubation and ventilation through an endotracheal tube is described, along with the clinical scenarios where it may be most applicable. Complications associated with intubation, with endotracheal or tracheostomy tubes, and with use of a mechanical ventilator are described as the major categories of complications associated with intubation and mechanical ventilation. Options for chronic ventilatory support in the home setting are presented, focusing primarily on home noninvasive ventilation. In selected patients with severe lung disease of various etiologies, lung transplantation may be an option, although it does replace the underlying disease with the potential complications of infection and rejection following transplantation.

Chapter 11 covers a wide range of diffuse parenchymal or interstitial lung diseases without a known etiologic agent triggering the disease. Idiopathic pulmonary fibrosis (IPF), a generally progressive disease with a relatively poor prognosis, is the most common entity within a broader category of idiopathic interstitial pneumonias. Also classified as an idiopathic interstitial pneumonia is nonspecific interstitial pneumonia (NSIP), which is commonly associated with underlying systemic rheumatic disease but can also be idiopathic. Two other entities within this category are desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-interstitial lung disease (RB-ILD), which are likely related and notable for a strong association with smoking. Rounding out the category of idiopathic interstitial pneumonias are two other disorders, cryptogenic organizing pneumonia (COP) and acute interstitial pneumonia (AIP). Sarcoidosis, a systemic granulomatous disease of unknown etiology, most commonly affects the lungs and/or intrathoracic lymph nodes, and is notable for a variable prognosis and the potential for therapeutic suppression of disease with corticosteroids. The chapter concludes by summarizing what is known about the pathogenesis and clinical aspects of several miscellaneous disorders involving the pulmonary parenchyma. These include pulmonary Langerhans cell histiocytosis (also called eosinophilic granuloma of the lung), lymphangioleiomyomatosis, Goodpasture syndrome, granulomatosis with polyangiitis, chronic eosinophilic pneumonia, and pulmonary alveolar proteinosis.

The lungs do not act in isolation, but rather are part of an integrated system that also involves the central nervous system (CNS), which controls the action of the muscles of respiration, and the appropriate response of the respiratory muscles to the signals they receive from the CNS. The respiratory generator, located in the medulla, also receives input from the cerebral cortex and higher levels of the brainstem, as well as feedback from central and peripheral chemoreceptors that is targeted to maintaining stable and acceptable levels of Po 2 and Pco 2 . This chapter provides an overview of the neural, muscular, and chest wall contributions to respiration. The anatomy of ventilatory control is presented, followed by a description of input that the control system receives from chemoreceptors as well as receptors from the lungs and chest wall. The action of the diaphragm, the main muscle of respiration, is described, including the importance of the zone of apposition and diaphragm length. This presentation of the anatomy and physiology of ventilatory control and the respiratory pump forms the background information for understanding the disorders of ventilatory control and disorders of the respiratory pump that will be presented in Chapters 18 and 19, respectively.

Chapter 6 reviews the common problem of chronic obstructive pulmonary disease (COPD). The various factors contributing to the etiology and pathogenesis of smoking are described, focusing on smoking and the protease-antiprotease hypothesis, but also considering environmental and indoor pollution, infection, and genetic factors. The pathologic features of chronic bronchitis and emphysema are detailed, including the contribution of small airways disease and the distinction between centrilobular and panacinar emphysema. The pathophysiology of airflow obstruction in COPD is explained, with consideration of factors that affect, as well as the effects of, airway resistance and loss of elastic recoil. Various factors potentially contributing to hypoxemia and hypercapnia are described, noting the importance of ventilation-perfusion mismatch. Newer concepts of COPD phenotypes are considered, as well as the factors that can lead to pulmonary hypertension in some patients. Treatment of COPD focuses on the use and roles of β 2 -agonists, anticholinergic agents, inhaled and systemic corticosteroids, antibiotics, and PDE-4 inhibitors. Lung volume reduction surgery and lung transplantation are considered as treatment options in selected individuals with severe disease, and the roles of pulmonary rehabilitation and long-term oxygen therapy are reviewed.

Chapter 12 reviews the anatomy and physiology of the pulmonary vasculature. In contrast to the systemic arteries, which carry blood from the left ventricle to the rest of the body, the pulmonary arteries, which carry blood from the right ventricle into the lungs, are relatively low-pressure, thin-walled vessels. Under normal circumstances, the mean pressure within the main pulmonary arteries is approximately 15 mm Hg, roughly one-sixth of the pressure in the aorta. Pulmonary hemodynamics are measured clinically by means of a balloon-tipped catheter inserted in a large systemic vein and advanced to a wedged position in the pulmonary vasculature. Geographic matching of ventilation and perfusion in the lung is essential for appropriate oxygen exchange and is accomplished in large part via hypoxic pulmonary vasoconstriction, by which blood flow in the lungs is preferentially routed to well ventilated alveoli. The pulmonary capillary endothelium also has important metabolic functions, such as the conversion of angiotensin I to angiotensin II.

Chapter 20 addresses the etiologic and pathologic aspects of lung cancer—the most common cause of cancer and cancer-related death worldwide. Risk factors, including smoking, occupational exposures and genetic predisposition, are explained. Concepts of the underlying pathogenesis of lung cancer are discussed, including the potential importance of proto-oncogenes and tumor suppressor genes. Detailed descriptions of the anatomic and pathological patterns of four major categories of lung cancer, squamous cell carcinoma, small cell carcinoma, adenocarcinoma, and large cell carcinoma, are examined.

Background Unexplained dyspnea is a common diagnosis that often results in repeated diagnostic testing and even delayed treatments while a determination of the cause is being investigated. Through a retrospective study, we evaluated the diagnostic efficacy of a multidisciplinary dyspnea evaluation center (MDEC) using invasive cardiopulmonary exercise test to diagnose potential causes of unexplained dyspnea. Methods We reviewed the medical records of all patients referred with unexplained dyspnea to the MDEC between March 2011 and October 2014. We assessed the diagnostic efficacy before and after presentation to the MDEC. Results During the study period a total of 864 patients were referred to the MDEC and, of those, 530 patients underwent further investigation with invasive cardiopulmonary exercise test and constituted the study sample. The median age was 57 (44-68) years, 67.2% were women, and median body mass index was 26.22 (22.78-31.01). A diagnosis was made in 530 patients including: exercise pulmonary arterial hypertension of 88 (16.6%), heart failure with preserved ejection fraction of 94 (17.7%), dysautonomia 112 (21.1%), oxidative myopathy of 130 (24.5%), primary hyperventilation of 43 (8.1%), and other 58 (10.9%). The time from initial presentation to referral was significantly longer than time to diagnosis after referral for non-standardized conventional methods versus diagnosis through MDEC using invasive cardiopulmonary exercise test (511 days (292-1095 days) vs. 27 days (13-53 days), p 0.0001). In a subgroup analysis, we reviewed that patients referred from cardiovascular clinics were more likely to have a greater number of diagnostic tests performed and, conversely, patients referred from pulmonary clinics were more likely to have a greater number of treatments prescribed before referral to MDEC. Conclusions As a result of this retrospective study, we have evaluated that a multidisciplinary approach that includes invasive cardiopulmonary exercise test dramatically reduces the time to diagnosis compared with traditional treatment and testing methods.

Increasingly over the past decade, faculty in medical and graduate schools have received requests from digital millennial learners for concise faculty-made educational videos. At our institution, over the past couple of years alone, several hundred educational videos have been created by faculty who teach in a flipped-classroom setting of the pre-clinical medical school curriculum. Despite the appeal and potential learning benefits of digital chalk-talk videos first popularized by Khan Academy, we have observed that the conceptual and technological barriers for creating chalk-talk videos can be high for faculty. To this end, this tips article offers an easy-to-follow 12-step conceptual framework to guide at-home production of chalk-talk educational videos.

Background Patients with severe pulmonary arterial hypertension (PAH) face significant morbidity and death as a consequence of progressive right heart failure. Surgical shunt placement between the left PA and descending aorta (Potts shunt) appears promising for PAH palliation in children; however, surgical mortality is likely to be unacceptably high in adults with PAH. Methods We describe a technique for transcatheter Potts shunt (TPS) creation by fluoroscopically guided retrograde needle perforation of the descending aorta at the site of apposition to the left PA to create a tract for deployment of a covered stent between these vessels. This covered stent—anchored by the vessel walls and surrounding tissue—serves as the shunt. Results TPS creation was considered in 7 patients and performed in 4. The procedure was technically successful in 3 patients; 1 patient died during the procedure as a result of uncontrolled hemothorax. One acute survivor, critically ill at the time of TPS creation, later died of comorbidities. The 2 mid-term survivors (follow-up of 10 and 4 months) are well at home, with symptomatic improvement and no late complications. The 3 candidate patients in whom the procedure was not performed died within 1 month of consideration, underscoring the tenuous nature of this population. Conclusions TPS creation is feasible and may offer symptomatic relief to select patients with refractory PAH. Further study of this innovative approach is warranted.

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease mediated by an immunological response to an inhaled antigen. Outbreaks of HP have been reported in industrial settings where manufacturing workers are exposed to water-based metalworking fluids (MWFs). Water-based MWFs promote growth of microorganisms and can be easily aerosolized and are thus potential aetiological agents of HP. We present a case of HP caused by exposure to water-based MWF in a vocational high school teacher. Culture of MWF used at his school grew Pseudomonas pseudoalcaligenes. This is the first known report of MWF-induced HP outside an industrial setting. The growth of Pseudomonas spp in this case recalls the earliest reports of the microbiology of MWF-induced HP and suggests that routine bacterial culture may be useful in the diagnosis of HP in workplaces without standard cleaning and biocide regulations.

Pregnancy outcomes in patients with pulmonary hypertension remain poor despite advanced therapies. Although consensus guidelines recommend against pregnancy in pulmonary hypertension, it may nonetheless occasionally occur. This guideline document sought to discuss the state of knowledge of pregnancy effects on pulmonary vascular disease and to define usual practice in avoidance of pregnancy and pregnancy management. This guideline is based on systematic review of peer-reviewed, published literature identified with MEDLINE. The strength of the literature was graded, and when it was inadequate to support high-level recommendations, consensus-based recommendations were formed according to prespecified criteria. There was no literature that met standards for high-level recommendations for pregnancy management in pulmonary hypertension. We drafted 38 consensus-based recommendations on pregnancy avoidance and management. Further, we identified the current state of knowledge on the effects of sex hormones during pregnancy on the pulmonary vasculature and right heart and suggested areas for future study. There is currently limited evidence-based knowledge about both the basic molecular effects of sex hormones and pregnancy on the pulmonary vasculature and the best practices in contraception and pregnancy management in pulmonary hypertension. We have drafted 38 consensus-based recommendations to guide clinicians in these challenging topics, but further research is needed in this area to define best practices and improve patient outcomes.

Study objectives: The effects of inhaled nitric oxide (NO) on hemodynamics and right ventricular (RV) contractility were compared with those of nitroprusside and nifedipine in 14 patients with severe chronic pulmonary hypertension. Study design: Micromanometer and balloon-tipped right heart catheterization were performed. Inhaled NO, IV nitroprusside, and sublingual nifedipine were administered sequentially while patients breathed > 90% oxygen. Setting: Cardiac catheterization laboratory in a tertiary care teaching hospital. Patients: Fourteen patients with severe pulmonary hypertension unrelated to left ventricular dysfunction. Measurements and results: During NO inhalation, mean systemic arterial pressure (MAP) was unchanged, but pulmonary artery (PA) pressure ([mean 6 SEM] 49 6 2m m Hg vs 446 2m m Hg; p< 0.01), pulmonary vascular resistance (PVR; 829 6 68 vs 669 6 64 dyne z s z cm 25 ;p < 0.01) and RV end-diastolic pressure (RVEDP; 12 6 1v s 106 1 mm Hg; p < 0.01) decreased. Stroke volume index (SVI; 31 6 2v s 35 6 3m L/m 2 ;p < 0.05) increased, and the first derivative of RV pressure at 15 mm Hg developed pressure (RV 1dP/dt at DP15) was unchanged. During nitroprusside administration, MAP decreased (105 6 5v s 766 5m m Hg; p< 0.01), PA was unchanged (48 6 2v s 456 3m m Hg; p5 not significant), and PVR decreased (791 6 53 vs 665 6 53 dyne z s z cm 25 ;p < 0.01). RV 1dP/dt at DP15 increased (425 6 22 vs 465 6 29 mm Hg/s; p < 0.05), but SVI was unchanged. Nifedipine decreased MAP (103 6 5v s 946 5m m Hg; p< 0.01), PA and PVR were unchanged, RVEDP increased (12 6 1v s 14 6 2m m Hg; p< 0.01), and RV 1dP/dt at DP15 decreased (432 6 90 vs 389 6 21 mm Hg/s; p < 0.05). Conclusions: Inhaled NO is a selective pulmonary vasodilator in patients with chronic pulmonary hypertension that improves cardiac performance without altering RV contractility. Nitroprusside caused a similar degree of pulmonary vasodilation. In contrast to inhaled NO, nitroprusside caused systemic hypotension associated with an increase in RV contractility. Acute administration of nifedipine did not cause pulmonary vasodilation, but RVEDP increased and RV contractility decreased. (CHEST 2001; 119:128‐136)

Extrinsic compression of the left main coronary artery can occur in patients with severe pulmonary hypertension and enlarged pulmonary artery trunk. It has been usually described in the setting of congenital defects such as atrial septal defect, ventricular septal defect, and, more rarely, isolated persistent ductus arteriosus. Functional and structural evaluation of such patients can currently be performed noninvasively with the use of cardiac CT scanning and/or MRI. The optimal management of symptomatic patients remains unknown. We report a case of extrinsic compression of the LMCA in a symptomatic patient with Eisenmenger syndrome who underwent unprotected LMCA stent implantation. We also performed a literature review of the reported cases concerning patients treated with LMCA stent implantation for the management of this condition.

Chapter 21 builds on the discussion of lung cancer presented in Chapter 20 , and focuses on clinical aspects and treatment. Symptoms of lung cancer may be due to local disease, metastatic disease, or paraneoplastic syndromes, and specific examples of each are addressed. The clinical evaluation of lung cancer usually starts with radiographic imaging—chest x-rays, computed tomography, and sometimes positron emission tomography. Tissue sampling is required for definitive diagnosis. The principles of lung cancer staging and treatment are considered. The chapter concludes with a brief discussion of bronchial carcinoid tumors, malignant mesothelioma, and the clinical problem of the solitary pulmonary nodule.

Chapter 2 covers the variety of major symptoms that can be experienced by patients with a disorder affecting the respiratory system. In many cases, it is one of these symptoms that leads to the individual's seeking medical care. Dyspnea, or shortness of breath, is a particularly common symptom that results from many acute and chronic pulmonary diseases, but it can also result from cardiovascular disease and a variety of other miscellaneous conditions. Cough, which is normally an important protective mechanism for clearing the airway, can be due to airway irritants, diseases affecting the airways or pulmonary parenchyma, heart failure, and a variety of miscellaneous causes, including use of angiotensin-converting inhibitors. Hemoptysis, which is most commonly from airways disease, can also be a consequence of pulmonary parenchymal or vascular disease. Chest pain, although most commonly resulting from cardiac disease, can occur with irritation, inflammation, or infiltration of pleural, diaphragmatic, or mediastinal surfaces.

This chapter continues the discussion of infectious diseases involving the lungs, and considers miscellaneous infections caused by fungi and Pneumocystis . For some of the organisms discussed, infection is a common potential problem for the individual with intact immunologic defense mechanisms. Histoplasmosis, coccidioidomycosis, and blastomycosis are the major fungal infections in this category, yet even for these diseases, impairment of normal defense mechanisms may substantially alter the presentation, clinical consequences, and natural history of the illness. For many other fungi and for Pneumocystis , the normal host is essentially protected from the organism. Disease occurs almost exclusively as a consequence of an underlying illness or a breakdown of normal defense mechanisms. Aspergillus is perhaps the most important fungus of this sort and is the main one considered in this chapter. Pneumocystis also is considered in this chapter.

Chapter 27 addresses acute and chronic respiratory failure. Respiratory failure is defined as a clinical state in which the respiratory system is not functioning adequately to keep gas exchange (i.e. blood gas values) at an acceptable level. The chapter discusses two types of respiratory failure: hypoxemic and hypercapnic respiratory failure. Because hypercapnia is often accompanied by hypoxemia, the term hypercapnic/hypoxemic respiratory failure is often used. Common causes of hypoxemic respiratory failure include severe pneumonia and acute respiratory distress syndrome (ARDS). Common causes of hypercapnic/hypoxemic respiratory failure include central nervous system depression, diseases of the respiratory muscles, and chronic obstructive pulmonary disease (COPD). Clinical findings in patients with respiratory failure typically include dyspnea, impaired mental status, cyanosis, and headache.

Chapter 1 provides the fundamentals of pulmonary anatomy and physiology that are critical for understanding both the normal functioning of the lung and the mechanisms for its disruption in the various disease states discussed throughout the book. After a presentation of basic lung anatomy, the relationships between pressure and volume within various compartments of the thorax are explored. An extensive discussion of how ventilation and circulation interact in oxygen uptake and carbon dioxide elimination by the lungs is followed by an explanation of how the relationship between ventilation and perfusion affects gas exchange. The chapter concludes with an explanation of the mechanisms behind abnormal gas exchange resulting in hypoxemia or hypercapnia.