- •Table of Contents
- •Copyright
- •Dedication
- •Introduction to the eighth edition
- •Online contents
- •List of Illustrations
- •List of Tables
- •1. Pulmonary anatomy and physiology: The basics
- •Anatomy
- •Physiology
- •Abnormalities in gas exchange
- •Suggested readings
- •2. Presentation of the patient with pulmonary disease
- •Dyspnea
- •Cough
- •Hemoptysis
- •Chest pain
- •Suggested readings
- •3. Evaluation of the patient with pulmonary disease
- •Evaluation on a macroscopic level
- •Evaluation on a microscopic level
- •Assessment on a functional level
- •Suggested readings
- •4. Anatomic and physiologic aspects of airways
- •Structure
- •Function
- •Suggested readings
- •5. Asthma
- •Etiology and pathogenesis
- •Pathology
- •Pathophysiology
- •Clinical features
- •Diagnostic approach
- •Treatment
- •Suggested readings
- •6. Chronic obstructive pulmonary disease
- •Etiology and pathogenesis
- •Pathology
- •Pathophysiology
- •Clinical features
- •Diagnostic approach and assessment
- •Treatment
- •Suggested readings
- •7. Miscellaneous airway diseases
- •Bronchiectasis
- •Cystic fibrosis
- •Upper airway disease
- •Suggested readings
- •8. Anatomic and physiologic aspects of the pulmonary parenchyma
- •Anatomy
- •Physiology
- •Suggested readings
- •9. Overview of diffuse parenchymal lung diseases
- •Pathology
- •Pathogenesis
- •Pathophysiology
- •Clinical features
- •Diagnostic approach
- •Suggested readings
- •10. Diffuse parenchymal lung diseases associated with known etiologic agents
- •Diseases caused by inhaled inorganic dusts
- •Hypersensitivity pneumonitis
- •Drug-induced parenchymal lung disease
- •Radiation-induced lung disease
- •Suggested readings
- •11. Diffuse parenchymal lung diseases of unknown etiology
- •Idiopathic pulmonary fibrosis
- •Other idiopathic interstitial pneumonias
- •Pulmonary parenchymal involvement complicating systemic rheumatic disease
- •Sarcoidosis
- •Miscellaneous disorders involving the pulmonary parenchyma
- •Suggested readings
- •12. Anatomic and physiologic aspects of the pulmonary vasculature
- •Anatomy
- •Physiology
- •Suggested readings
- •13. Pulmonary embolism
- •Etiology and pathogenesis
- •Pathology
- •Pathophysiology
- •Clinical features
- •Diagnostic evaluation
- •Treatment
- •Suggested readings
- •14. Pulmonary hypertension
- •Pathogenesis
- •Pathology
- •Pathophysiology
- •Clinical features
- •Diagnostic features
- •Specific disorders associated with pulmonary hypertension
- •Suggested readings
- •15. Pleural disease
- •Anatomy
- •Physiology
- •Pleural effusion
- •Pneumothorax
- •Malignant mesothelioma
- •Suggested readings
- •16. Mediastinal disease
- •Anatomic features
- •Mediastinal masses
- •Pneumomediastinum
- •Suggested readings
- •17. Anatomic and physiologic aspects of neural, muscular, and chest wall interactions with the lungs
- •Respiratory control
- •Respiratory muscles
- •Suggested readings
- •18. Disorders of ventilatory control
- •Primary neurologic disease
- •Cheyne-stokes breathing
- •Control abnormalities secondary to lung disease
- •Sleep apnea syndrome
- •Suggested readings
- •19. Disorders of the respiratory pump
- •Neuromuscular disease affecting the muscles of respiration
- •Diaphragmatic disease
- •Disorders affecting the chest wall
- •Suggested readings
- •20. Lung cancer: Etiologic and pathologic aspects
- •Etiology and pathogenesis
- •Pathology
- •Suggested readings
- •21. Lung cancer: Clinical aspects
- •Clinical features
- •Diagnostic approach
- •Principles of therapy
- •Bronchial carcinoid tumors
- •Solitary pulmonary nodule
- •Suggested readings
- •22. Lung defense mechanisms
- •Physical or anatomic factors
- •Antimicrobial peptides
- •Phagocytic and inflammatory cells
- •Adaptive immune responses
- •Failure of respiratory defense mechanisms
- •Augmentation of respiratory defense mechanisms
- •Suggested readings
- •23. Pneumonia
- •Etiology and pathogenesis
- •Pathology
- •Pathophysiology
- •Clinical features and initial diagnosis
- •Therapeutic approach: General principles and antibiotic susceptibility
- •Initial management strategies based on clinical setting of pneumonia
- •Suggested readings
- •24. Bacterial and viral organisms causing pneumonia
- •Bacteria
- •Viruses
- •Intrathoracic complications of pneumonia
- •Respiratory infections associated with bioterrorism
- •Suggested readings
- •25. Tuberculosis and nontuberculous mycobacteria
- •Etiology and pathogenesis
- •Definitions
- •Pathology
- •Pathophysiology
- •Clinical manifestations
- •Diagnostic approach
- •Principles of therapy
- •Nontuberculous mycobacteria
- •Suggested readings
- •26. Miscellaneous infections caused by fungi, including Pneumocystis
- •Fungal infections
- •Pneumocystis infection
- •Suggested readings
- •27. Pulmonary complications in the immunocompromised host
- •Acquired immunodeficiency syndrome
- •Pulmonary complications in non–HIV immunocompromised patients
- •Suggested readings
- •28. Classification and pathophysiologic aspects of respiratory failure
- •Definition of respiratory failure
- •Classification of acute respiratory failure
- •Presentation of gas exchange failure
- •Pathogenesis of gas exchange abnormalities
- •Clinical and therapeutic aspects of hypercapnic/hypoxemic respiratory failure
- •Suggested readings
- •29. Acute respiratory distress syndrome
- •Physiology of fluid movement in alveolar interstitium
- •Etiology
- •Pathogenesis
- •Pathology
- •Pathophysiology
- •Clinical features
- •Diagnostic approach
- •Treatment
- •Suggested readings
- •30. Management of respiratory failure
- •Goals and principles underlying supportive therapy
- •Mechanical ventilation
- •Selected aspects of therapy for chronic respiratory failure
- •Suggested readings
- •Index
Pneumocystis infection
Although Pneumocystis jiroveci (formerly called Pneumocystis carinii) has been recognized for decades as a cause of pneumonia in immunocompromised patients, its clinical importance as a major pathogen in patients with HIV/AIDS sparked renewed interest in the organism, its treatment, and prevention of infection in high-risk patients. The use of combination antiretroviral therapy (cART) regimens to treat HIV and preserve immune system function has considerably decreased the number of AIDS-related Pneumocystis cases. Nevertheless, it remains an important pulmonary pathogen, not only in HIV-infected patients but also in a variety of other immunosuppressed patients.
The taxonomy of Pneumocystis has changed a number of times since its discovery in 1909. For many years, the organism was considered a protozoan, but techniques involving nucleic acid sequencing of ribosomal RNA and studies of enzyme structure and cell wall composition have shown that the organism is more closely related to fungi than to protozoa. Pneumocystis is now classified as a unique category of fungi. The nomenclature change of P. carinii to P. jiroveci recognizes the pathologist Otto Jirovec, who first described the organism in humans.
Features of Pneumocystis jiroveci:
1.Ubiquitous distribution
2.Seen on methenamine silver stain rather than routine tissue and Gram stains
3.Tissue response in the lung is primarily exudation of foamy fluid into alveoli
Pneumocystis appears to be widely distributed in nature. Normally, it can be found in the lungs of a variety of animals as well as in humans. Yet the organisms only cause disease in individuals with impaired cellular immunity. The key cell appears to be the helper T lymphocyte CD4+, whose numbers, function, or both can be diminished by specific diseases or immunosuppressive drugs. Before the recognition of HIV/AIDS, P. jiroveci pneumonia was seen most commonly in patients with severe malnutrition, malignancy, organ transplantation, or other diseases requiring treatment with corticosteroids or other immunosuppressive agents. However, after the identification of AIDS and before the introduction of cART, the majority of cases were seen in patients with AIDS and greatly reduced numbers of CD4+ lymphocytes. The problem of Pneumocystis pneumonia as it occurs in AIDS is discussed in more detail in Chapter 27.
Pneumocystis cysts, which are seen in the lung tissue of infected patients, appear on light-microscopic examination as round or cup-shaped structures. They do not stain well with routine hematoxylin and eosin stains and require special stains, such as methenamine silver (Fig. 26.2). The tissue response to the organism seen on microscopic examination of lung tissue includes infiltration of mononuclear cells within the pulmonary interstitium and exudation of foamy fluid (containing cysts) into alveolar spaces. An exuberant host inflammatory response to the organism contributes to the pulmonary injury. As a result, many patients with Pneumocystis pneumonia are treated with corticosteroids in addition to antimicrobial therapy against Pneumocystis early in the course of the disease to suppress this transiently deleterious response.
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FIGURE 26.2 High-power photomicrograph of many Pneumocystis cysts as seen
with methenamine silver staining. Darkly staining cysts are within the alveolar
lumen. Note the foamy exudate in the alveolar lumen.
Clinically, Pneumocystis pneumonia usually manifests with cough, dyspnea, and fever in immunocompromised patients. Notably, in patients for whom treatment with corticosteroids was the risk factor for developing Pneumocystis pneumonia, symptoms frequently develop (and the infection is recognized) as the dose of corticosteroids is being tapered. This observation further supports the concept that the host inflammatory reaction to the organism, which is suppressed by corticosteroids and surges only as the corticosteroid dose is being tapered, is responsible for much of the clinical presentation. The chest radiograph commonly shows diffuse bilateral infiltrates, which can have the appearance of either an interstitial or an alveolar filling pattern (Fig. 26.3). Alveolar filling and resultant areas of shunting often make hypoxemia a particularly prominent clinical feature in these patients. Although the disease is often insidious in onset in AIDS patients, it commonly manifests in other immunocompromised patients as a relatively acute-onset pneumonia that, if untreated, can rapidly progress to respiratory failure and death within days.
FIGURE 26.3 Chest radiograph of a patient with AIDS and pneumonia due to
Pneumocystis jiroveci. Infiltrates representing the alveolar filling are most
prominent at the right base, but also appear in the left midlung field as diffuse
haziness.
Clinical features of Pneumocystis pneumonia:
1.Symptoms: cough, dyspnea, fever
2.Chest radiograph: frequently diffuse interstitial or alveolar infiltrates
3.Hypoxemia
Because the organism is extremely difficult to cultivate in the laboratory setting, diagnosis depends on demonstrating the organism on stains of tissue sections, BAL fluid, or sputum that has been induced by having the patient inhale a hypertonic saline aerosol. The use of monoclonal antibodies and polymerase chain reaction technology as a means of detecting the organism in sputum or BAL fluid has improved the detection rate compared with the use of previous staining methods. No serologic or skin testing methods are available for diagnosis. A positive β-D-glucan assay is observed in many patients and is a useful adjunctive test; a negative test has good predictive value.
The treatment of choice for Pneumocystis infection is a combination of trimethoprim and sulfamethoxazole. Primaquine/clindamycin, pentamidine, atovaquone, or one of several other regimens are alternative options in patients who cannot tolerate trimethoprim-sulfamethoxazole. In high-risk patients, such as transplant recipients or individuals receiving antineoplastic chemotherapy for leukemia,
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low doses of the same agents are used prophylactically to prevent the infection.
Suggested readings
Fungal infections (general references)
Azar M.M, Malo J. & Hage C.A. Endemic fungi presenting as community-acquired pneumonia: A review Seminars in Respiratory and Critical Care Medicine 2020;41: 522537.
Godoy M.C.B, Ferreira Dalla Pria H.R, Truong M.T, Shroff G.S. & Marom E.M. Invasive fungal pneumonia in immunocompromised patients Radiologic Clinics of North America 2022;60: 497-506.
Kanne J.P. North American endemic fungal infections Radiologic Clinics of North America 2022;60: 409-427.
Khandelwal N, Sodhi K.S, Sinha A, Reddy J.G. & Chandra E.N. Multidetector computed tomography and MR imaging findings in mycotic infections Radiologic Clinics of North America 2016;54: 503-518.
Lewis R.E. Current concepts in antifungal pharmacology Mayo Clinic Proceedings 2011;86: 805-817.
Limper A.H, Knox K.S, Sarosi G.A, Ampel N.M, Bennett J.E, Catanzaro A., et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients American Journal of Respiratory and Critical Care Medicine 2011;183: 96-128.
Histoplasmosis
Azar M.M. & Hage C.A. Laboratory diagnostics for histoplasmosis Journal of Clinical Microbiology 2017;55: 1612-1620.
Azar M.M, Loyd J.L, Relich R.F, Wheat L.J. & Hage C.A. Current concepts in the epidemiology, diagnosis, and management of histoplasmosis syndromes Seminars in Respiratory and Critical Care Medicine 2020;41: 13-30.
Myint T, Anderson A.M, Sanchez A, Farabi A, Hage C, Baddley J.W., et al. Histoplasmosis in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS): Multicenter study of outcomes and factors associated with relapse Medicine (Baltimore) 2014;93: 11-18.
Wheat L.J, Azar M.M, Bahr N.C, Spec A, Relich R.F. & Hage C. Histoplasmosis Infectious Disease Clinics of North America 2016;30: 207-227.
Coccidioidomycosis
Bays D.J. & Thompson G.R.III. Coccidioidomycosis Infectious Disease Clinics of North America 2021;35: 453-469.
Crum N.F. Coccidioidomycosis: A contemporary review Infectious Diseases and Therapy 2022;11: 713-742.
Galgiani J.N, Ampel N.M, Blair J.E, Catanzaro A, Geertsma F, Hoover S.E., et al. 2016
Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis Clinical Infectious Diseases 2016;63: e112e146.
Kimes K.E, Kasule S.N. & Blair J.E. Pulmonary coccidioidomycosis Seminars in Respiratory and Critical Care Medicine 2020;41: 42-52.
Odio C.D, Marciano B.E, Galgiani J.N. & Holland S.M. Risk factors for disseminated coccidioidomycosis, United States Emerging Infectious Diseases 2017;23: 308-311.
Blastomycosis
Kaka A.S. & Sarosi G.A. Disseminated blastomycosis New England Journal of Medicine 6, 2017;376: e9.
Linder K.A. & Kauffman C.A. Current and new perspectives in the diagnosis of blastomycosis and histoplasmosis Journal of Fungi 2020;7: 12.
Mazi P.B, Rauseo A.M. & Spec A. Blastomycosis Infectious Disease Clinics of North America 2021;35: 515-530.
Schwartz I.S, Embil J.M, Sharma A, Goulet S. & Light R.B. Management and outcomes of acute respiratory distress syndrome caused by blastomycosis: A retrospective case series
Medicine (Baltimore) 2016;95: e3538.
Aspergillosis
Agarwal R, Muthu V, Sehgal I.S, Dhooria S, Prasad K.T. & Aggarwal A.N. Allergic bronchopulmonary aspergillosis Clinics in Chest Medicine 2022;43: 99-125.
Cadena J, Thompson G.R,III & Patterson T.F. Aspergillosis: Epidemiology, diagnosis, and treatment Infectious Disease Clinics of North America 2021;35: 415-434.
Denning D.W, Cadranel J, Beigelman-Aubry C, Ader F, Chakrabarti A, Blot S., et al. Chronic pulmonary aspergillosis: Rationale and clinical guidelines for diagnosis and management European Respiratory Journal 2016;47: 45-68.
Kosmidis C. & Denning D.W. The clinical spectrum of pulmonary aspergillosis Thorax 2015;70: 270-277.
Patterson K.C. & Strek M.E. Diagnosis and treatment of pulmonary aspergillosis syndromes
Chest 2014;146: 1358-1368.
Walsh T.J, Anaissie E.J, Denning D.W, Herbrecht R, Kontoyiannis D.P, Marr K.A., et al.
Treatment of aspergillosis: Clinical practice guidelines of the Infectious Diseases Society of America Clinical Infectious Diseases 2008;46: 327-360.
Pneumocystis infection
Alanio A, Hauser P.M, Lagrou K, Melchers W.J, Helweg-Larsen J, Matos O., et al. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients Journal of Antimicrobial Chemotherapy 2016;71: 2386-2396.
Avino L.J, Naylor S.M. & Roecker A.M. Pneumocystis jirovecii pneumonia in the non-HIV- infected population Annals of Pharmacotherapy 2016;50: 673-679.
Fishman J.A. Pneumocystis jiroveci Seminars in Respiratory and Critical Care Medicine
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2020;41: 141-157.
Proudfoot R, Phillips B. & Wilne S. Guidelines for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) in children with solid tumors Journal of Pediatric Hematology/Oncology 2017;39: 194-202.
Senécal J, Smyth E, Del Corpo O, Hsu J.M, Amar-Zifkin A, Bergeron A., et al. Non-invasive diagnosis of Pneumocystis jirovecii pneumonia: A systematic review and meta-analysis
Clinical Microbiology and Infection 2022;28: 23-30.
Siegel M, Masur H. & Kovacs J. Pneumocystis jirovecii pneumonia in human immunodeficiency virus infection Seminars in Respiratory and Critical Care Medicine 2016;37: 243-256.
Weyant R.B, Kabbani D, Doucette K, Lau C. & Cervera C. Pneumocystis jirovecii: A review with a focus on prevention and treatment Expert Opinion on Pharmacotherapy 2021;22: 1579-1592.