Search

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).

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.

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 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.

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.

During the last several decades, physicians have been faced with increasing numbers of patients who have impaired host defense mechanisms, particularly due to infection with the human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS). In addition, neutropenia (decreased polymorphonuclear leukocytes) or depressed cellular immunity occurs frequently as a result of either chemotherapy given for malignancy or immunosuppressive agents administered for inflammatory diseases or suppression of rejection following organ transplantation. This chapter is devoted to the spectrum of respiratory complications potentially associated with several of the more commonly encountered forms of immunodeficiency. Immunocompromised patients are extremely susceptible to respiratory tract infections with a variety of organisms, some of which rarely cause disease in the immunocompetent host. When the immunosuppressed patient has fever and new pulmonary infiltrates, the possibility of an “opportunistic” infection comes immediately to mind. However, immunocompromised patients are also susceptible to common respiratory pathogens and noninfectious complications, both of which must be seriously considered in the differential diagnosis.

Nitric oxide (NO) signaling plays a key role in modulating vascular tone and remodeling in the pulmonary circulation. The guanylate cyclase/cyclic guanylate monophosphate-signaling pathway primarily mediates nitric oxide signaling. This pathway is critical in normal regulation of the pulmonary vasculature, and is an important target for therapy in patients with pulmonary hypertension. In the pulmonary vasculature, degradation of cGMP is primarily regulated by PDE-5, and inhibition of this enzyme has important effects on pulmonary vasculature smooth muscle tone. Large randomized placebo-controlled trials of PDE-5 inhibitors demonstrated improved exercise capacity, hemodynamics and quality of life in adult patients with PAH. This chapter will discuss the mechanisms of NO signaling in the vasculature, characteristics of the PDE5-inhibitors approved for treatment of PH, and review available data on the use of phosphodiesterase inhibitors in PH.

The role of phospholipase A2 (PLA2) in lung injury in humans is unclear. Previous studies have failed to identify an increase in PLA2 activity in bronchoalveolar lavage fluids (BALF) of patients with the adult respiratory distress syndrome (ARDS). In this study, increased phospholipase A2 (PLA2) activity was detected in BALF from patients with ARDS. PLA2 levels in BALF correlated positively with lung injury score in patients with lung disease. BALF PLA2 activity in patients with ARDS was resolved into heparin binding and nonbinding activities. Both PLA2 activities were increased in BALF of ARDS patients. The PLA2 activity that bound to heparin was identified as a group II PLA2 by its chromatographic characteristics, its inhibition by dithiothreitol, its substrate specificity, and its approximate molecular mass of 14 kDa. The second PLA2 activity was further purified and found to require Ca2+ at a concentration > 2 x 10(-4) M for activity. This form of PLA2 exhibited a neutral and broad pH optimum (pH 6.0-8.0) and hydrolyzed both phosphatidylethanolamine and phosphatidylcholine effectively. Its apparent molecular mass was estimated to be 80–90 kDa. Neither anti-pancreatic PLA2 antiserum nor anti-pig spleen cytosolic 100-kDa PLA2 antiserum immunoprecipitated the enzymatic activity. Thus at least two forms of PLA2 are increased in activity in BALF of patients with ARDS, a group II PLA2 and a biochemically and immunochemically form distinct from group I, group II, and cytosolic PLA2. Increased lung PLA2 activity may be important for the pathophysiology of ARDS.

Presentation of Case A 46-year-old man was admitted to the hospital because of a mass in the lower lobe of the left lung. The patient had been in excellent health until 15 weeks earlier, when he was in Florida visiting his father, who had an upper respiratory tract infection. The patient soon became febrile, with a cough productive of bloody sputum and mild exertional dyspnea. X-ray films of the chest 10 days after the onset of symptoms showed an ill-defined mass in the left lower lobe, and antibiotics were given, with complete resolution of symptoms. Twenty-seven days later radiographs of . . .

The risk for complications and death associated with pregnancy in patients with pulmonary hypertension remains prohibitive. This chapter will review the physiological changes associated with pregnancy, past and current reported experience in pregnancy associated with pulmonary arterial hypertension (PAH), the management of patients with PAH during pregnancy, and finally, the approach to contraception in patients with PAH. In general, the hemodynamic issues and outcomes in pregnancy associated with PAH are similar despite the primary cause of PAH. Thus, pregnancy in idiopathic PAH (iPAH), PAH related to congenital heart disease (PAH–CHD), and connective tissues diseases are considered together unless noted.

Chapter 7 covers several miscellaneous diseases affecting the airways. Bronchiectasis, the irreversible dilation of airways caused by inflammatory destruction of airway walls, is often due to infection or problems with airway clearance that result from obstruction or a defect in any of several host defense mechanisms. The various etiologies of bronchiectasis are presented, followed by the clinical and pathophysiologic features that are common to bronchiectasis, independent of etiology. Treatment focuses on the use of bronchodilators, antibiotics, and clearance of airway secretions. Cystic fibrosis, a genetic disorder most commonly associated with pulmonary and pancreatic disease, is discussed in detail, The various types of genetic mutations that can lead to cystic fibrosis are presented, along with a description of what is known about the abnormalities in ion transport across the airway wall that ultimately lead to thick, tenacious sputum and recurrent infection. Therapeutic modalities are described, including antibiotics, bronchopulmonary drainage, and newer options that are directed toward ameliorating the genetic abnormality or its direct effect on ion transport. Finally, the chapter discussed upper airway obstruction, emphasizing the differing effects of intrathoracic versus extrathoracic upper airway obstruction.

Chapter 4 focuses on airway anatomy and physiology, providing the background information about airway structure and function that will prove critical in understanding how normal structure and function are affected by diseases involving the airways, particularly asthma and chronic obstructive pulmonary disease. Airway anatomy and histology are presented, followed by a description of neural innervation of the airways and the effect of sympathetic, parasympathetic, and non-adrenergic, non-cholinergic stimulation on airway tone. A discussion of airway function covers the concept of airway resistance and explains the determinants of forced expiratory flow. The difficult conceptual model of the equal pressure point during forced expiration is explained, with implications for effort-dependent and effort-independent components of the forced expiratory flow-volume curve.

Chapter 19 addresses disorders affecting the respiratory pump including neuromuscular disease, disorders of the diaphragm, and disorders affecting the chest wall. Four of the more common neuromuscular diseases that influence the respiratory system are discussed: Guillain-Barre syndrome, myasthenia gravis, poliomyelitis, and amyotrophic lateral sclerosis. Respiratory muscle weakness, both inspiratory and expiratory, is the underlying pathophysiology for these disorders. The diaphragm is the most important inspiratory muscle of respiration, and this chapter reviews diaphragmatic muscle fatigue and both unilateral and bilateral diaphragmatic paralysis. Finally, two important processes affecting the chest wall, kyphoscoliosis and obesity, are discussed.

It has been estimated that approximately one-third of the world's current population, or over 2 billion people, have been infected (i.e., have either latent or active infection) with the tubercle bacillus, with approximately 10 million new cases of active tuberculosis and approximately 1.8 million deaths occurring worldwide each year. The overwhelming majority of cases of active tuberculosis occur in developing countries. Tuberculosis remains an important public health problem in the United States and other industrialized countries, particularly in indigent and immigrant populations and patients with AIDS. This chapter reviews the pathophysiology and clinical manifestations of tuberculosis, as well as diagnosis and management. The epidemiology, diagnosis, and treatment of disease caused by nontuberculous mycobacteria are also reviewed.

Chapter 18 builds on Chapter 17 and addresses disorders of ventilatory control. Hyperventilation, most frequently due to an acute disorder of the central nervous system, to a variety of pulmonary diseases, or to hormonal stimulation, is discussed. The primary mechanism leading to hyperventilation is either unknown or appears to be an increased sensitivity or stimulation of the central chemoreceptors or other receptors providing input to the respiratory generator. Hypoventilation disorders, including primary alveolar hypoventilation and congenital central hypoventilation, are reviewed. The pathophysiology of Cheynes-Stokes respiration, an abnormal breathing pattern characterized by cyclic hyper- and hypoventilation, is examined. Finally, obstructive sleep apnea (OSA) and central sleep apnea (CSA) and mixed syndromes are addressed. OSA is more common than CSA. Clinical features of sleep apnea include disordered respiration during sleep, hypersomnolence, morning headaches, and cardiovascular complications. Diagnosis and treatment are reviewed.

The acute respiratory distress syndrome (ARDS) is a syndrome of diffuse lung injury characterized by high permeability pulmonary edema, diffuse alveolar infiltrates, hypoxia, and reduced lung compliance that occurs within hours to days following a variety of precipitating conditions. ARDS is now understood as a characteristic response of the lung to injury, and as part of the multiple organ dysfunction syndrome (MODS). Despite extensive research into the pathogenesis and treatment of this disorder, our understanding remains incomplete and mortality remains high.

Nitric oxide (NO) reduces airway tone in the methacholine-treated guinea pig. We examined whether low levels of inhaled NO gas would relax airway smooth muscle tone in patients with mild asthma subjected to methacholine-induced bronchospasm. Thirteen adult volunteers with mild asthma inspired increasing concentrations of methacholine until their baseline forced expiratory volume in one second (FEV1, 3.29 +/- 0.17 L, mean +/- SEM) decreased by > or = 20% (2.33 +/- 0.18 L, p < 0.01). Thereafter, they sequentially inhaled 100 parts per million (ppm) NO, 40% O2; 40% O2; and 100 ppm NO, 40% O2 while spirometry was performed. Subsequent inhalation of isoproterenol returned the FEV1 levels to baseline. Inhaling 100 ppm NO increased FEV1 to 2.66 +/- 0.18 L (p < 0.01), and this increase was maintained after NO was discontinued. FEV1 did not change during the second period of NO inhalation. Similar results were observed for vital capacity, but no significant effect was noted on forced expiratory flow at 25% of vital capacity or peak expiratory flow. Subjects were then divided into a responder subgroup, which showed a mean increase in FEV1 after initial NO inhalation of 560 +/- 150 ml, and a nonresponder subgroup, which showed a mean increase in FEV1 of 129 +/- 29 ml. Our data suggest that inhalation of nitric oxide by patients with mild asthma with methacholine-induced bronchospasm results in a minor but significant relaxation of airway tone.

To characterize the evolution of inflammation in the adult respiratory distress syndrome (ARDS) and test the hypothesis that sustained alveolar inflammation is associated with a poor outcome in patients with ARDS, we performed fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) in 125 patients and compared BAL cells and protein concentrations in survivors and nonsurvivors. ARDS followed sepsis syndrome in 35 patients, major trauma in 41, and other causes in 49. When possible, BAL was performed on Days 3, 7, and 14 after the onset of ARDS. Sixty-five patients (52%) had more than one BAL. We first performed analyses on each BAL day using information from all 212 BAL in the 125 patients (cross-sectional analysis). All patients had increased leukocytes and total protein in the first BAL (Day 3 after onset of ARDS). In patients with ARDS following sepsis, the percentage of BAL polymorphonuclear leukocytes (PMN) was higher on Day 7 (p = 0.11) and particularly Day 14 (p = 0.02) in patients who died; there was a consistent trend of a higher PMN concentration on all days in patients who died then in those who lived. In patients with ARDS following trauma and other risks, however, BAL PMN measures did not distinguish survivors from patients who died. Analysis of serial data from the patients with more than one BAL showed that alveolar macrophages (AM) increased in survivors of ARDS, both in absolute numbers and as a percentage of total cells; this pattern was most pronounced in the sepsis patients. The cross-sectional data analysis suggests that sustained alveolar inflammation occurs frequently in patients with ARDS following sepsis and is associated with a high mortality.

The metabolic, hormonal and haemodynamic effects of oral pirbuterol, a new beta 2-adrenoceptor agonist, were studied acutely (n = 19) and after 3 months treatment (n = 11) in patients with severe heart failure receiving chronic frusemide therapy. In the acute study fasted patients (n = 10) showed reductions in plasma K+ (P less than 0.005) and cortisol (P less than 0.01) and increases in plasma glucose (P less than 0.005), insulin (P less than 0.01), lactate (P less than 0.005) and pyruvate (P less than 0.0025). These acute changes were less in unfasted subjects (n = 9). Maximal increase in stroke volume occurred at approximately half the plasma pirbuterol concentration required for maximal effect on plasma insulin. Treatment with pirbuterol for 3 months was associated with sustained increases in stroke volume and fasting plasma glucose and insulin, but there was loss of all other acute metabolic effects. Despite concurrent frusemide and digoxin therapy acute hypokalaemia caused no adverse effects. Hypokalaemia did not occur with chronic pirbuterol administration.

Objectives. This study was performed to assess the utility of inhaled nitric oxide as a selective pulmonary vasodilator in patients with seven chronic heart failure and to compare its hemodynamic effects with those of nitroprusside, a nonselective vasodilator. Background. Preoperative pulmonary vascular resistance is a predictor of right heart failure after heart transplantation. Nonselective vasodilators administered preoperatively to assess the reversibility of pulmonary vasoconstriction cause systemic hypotension, limiting their utility. Methods. Systemic and pulmonary hemodynamic measurements were made at baseline, during oxygen inhalation and with the addition of graded doses of inhaled nitric oxide or intravenous nitroprusside in 16 patients with New York Heart Association class III or IV heart failure referred for heart transplantation. Results. Pulmonary vascular resistance decreased to a greater extent with 80 ppm nitric oxide (mean ± SEM 256 ± 41 to 139 ± 14 dynes · s · cm−5) than with the maximally tolerated dose of nitroprasside (264 ± 49 to 169 ± 30 dynes · s · cm−5, p < 0.05, nitric oxide vs. nitroprusside). Pulmonary capillary wedge pressure increased with 80 ppm nitric oxide (26 ± 2 to 32 ± 2 mm Hg, p < 0.05). Mean arterial pressure did not change with nitric oxide but decreased with nitroprusside. Seven of the 16 patients, including 1 patient who did not have an adequate decrease in pulmonary vascular resistance with nitroprasside but did with nitric oxide, have undergone successful heart transplantation. Conclusions. Inhaled nitric oxide is a selective pulmonary vasodilator in patients with pulmonary hypertension due to left heart failure and may identify patients with reversible pulmonary vasoconstriction in whom agents such as nitroprusside cause systemic hypotension. Inhaled nitric oxide causes an increase in left ventricular filling pressure by an unknown mechanism.