Initial evaluation of diffuse pulmonary infiltrates frequently focuses on the diagnosis of Pneumocystis pneumonia in patients at high risk because of a CD4+ count less than 200/mm3, especially if they are not receiving adequate prophylaxis. An elevated serum β-D-glucan level also supports the diagnosis of Pneumocystis. Induction of sputum accompanied by appropriate staining for Pneumocystis is often the first diagnostic procedure because of its noninvasive nature. When sputum induction produces negative findings, flexible bronchoscopy is usually the next procedure performed, typically with BAL and sometimes with transbronchial biopsy. The yield for Pneumocystis is excellent with BAL, but making a diagnosis of some of the other infections, neoplasms, and inflammatory processes may require transbronchial biopsy. During bronchoscopy, Kaposi sarcoma is strongly suspected if typical lesions are observed in the airways. Surgical lung biopsy is the most invasive of the diagnostic procedures and is usually reserved for situations where a diagnosis is crucial but not forthcoming by less invasive means.

Pulmonary complications in non–HIV immunocompromised patients

Over the past several decades, increasing numbers of patients have been rendered immunocompromised due to organ transplantation, antineoplastic chemotherapy, or the use of immunosuppressive medications for inflammatory conditions. In addition, improved diagnostic tools have resulted in better identification of patients with primary disorders of one or more limbs of the immune system.

Organ transplant recipients

With very rare exceptions, organ transplantation necessitates some degree of suppression of the recipient’s immune system in order to prevent rejection of the transplanted organ. A necessary consequence of this immunosuppression is an increased risk of infection. Because the lungs communicate with the outside environment with every breath, pulmonary infections are very common in this population and are a major cause of morbidity and mortality following organ transplantation.

Solid organ transplantation

Lung transplantation is increasingly performed to treat a variety of end-stage lung diseases (see Chapter 30). In addition to the effects of immunosuppressive medications, the transplanted lung has impaired lymphatic drainage, decreased cough and mucociliary function, and constant exposure to organisms from the environment, all leading to an increased risk of a variety of types of pulmonary infection. The propensity of specific organisms to cause infections in the post–lung transplant period varies somewhat during the time course following transplantation.

In the first month after lung transplantation, pulmonary infections are most commonly caused by healthcare-associated pneumonia organisms such as Gram-negative rods and Staphylococcus aureus. Between months 1 and 6 after transplantation, patients are at maximal risk for opportunistic infections such as CMV, P. jiroveci, toxoplasmosis, Aspergillus, endemic fungi, and mycobacteria. By 6 months posttransplant, most patients are receiving stable and reduced levels of immunosuppression. These patients are most frequently subject to community-acquired pneumonias due to pneumococcus, Mycoplasma, Legionella, respiratory viruses (e.g., influenza, parainfluenza, RSV, adenovirus, and metapneumovirus), or other common respiratory pathogens. Information about the incidence and clinical course of COVID-19 infection in transplant recipients is evolving; however, full vaccination is required by most programs.

Similar patterns are observed among patients who receive transplants of other solid organs, such as the heart, liver, or kidney. However, the overall incidence of pneumonia is less common in these groups, both because their native lung defenses remain intact and because lower levels of immunosuppression are

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been reported. Diffuse bronchiectasis may develop due to repeated infections (see Chapter 7). If the bronchiectasis is sufficiently severe, hypoxemia and cor pulmonale may ultimately ensue. Amelioration of many manifestations of antibody deficiencies may be possible by regular administration of intravenous human IgG.

Cellular immunodeficiencies are characterized by either reduced T cell numbers or function. Cellular immunodeficiencies are observed in conditions such as DiGeorge syndrome (in which a deletion on chromosome 22 leads to thymic hypoplasia) or severe combined immunodeficiency syndrome, a heterogeneous group of conditions characterized by absent or severely impaired T-cell function and some element of concomitant B-cell hypofunction. Patients usually present in early infancy with recurrent gastrointestinal and pulmonary infections due to common and opportunistic pathogens (e.g., P. jiroveci), as well as thrush and impaired growth. Patients have a high mortality due to disseminated infections. HSCT from a human leukocyte antigen (HLA) identical donor is successful in reversing the immunodeficiency state in some patients.

Phagocytic cell disorders may also lead to recurrent pulmonary infections. For example, patients with chronic granulomatous disease lack NADPH oxidase function and frequently develop pulmonary infections due to catalase-positive organisms such as Aspergillus, S. aureus, and Burkholderia cepacia. Patients with hyper-IgE syndrome (also called Job syndrome) have defects in immunologic signaling pathways causing impaired T-cell function and leading to increased susceptibility to pulmonary infections due to S. aureus, H. influenzae, Aspergillus, and Pseudomonas.

Diagnostic evaluation of pulmonary infiltrates in non–HIV immunocompromised patients

As for patients with HIV infection, the approach to the non-HIV immunocompromised patient with pulmonary infiltrates revolves around the attempt to identify an infectious agent or noninfectious etiology. Because the differential diagnosis of pulmonary infiltrates in these patients is so broad, clues from the exposure history and radiographic patterns may be even more useful. Noninvasive assessment with antigen detection, PCR assays, β-1,3-glucan levels, sputum examination, and other tests is typically performed. However, invasive testing with specimens obtained by bronchoscopy or thoracoscopic lung biopsy may also be necessary. The procedure chosen is based on specific clinical features relevant to each patient, such as the nature of the underlying disease, suspected cause of the pulmonary infiltrate, presence or absence of other predisposing factors, and potential risks of a diagnostic procedure. However, in some immunocompromised patients with pulmonary infiltrates, empirical treatment is given without a definitive diagnosis, particularly when patients are at high risk for complications from invasive procedures.

The spectrum of infectious and noninfectious causes of pulmonary infiltrates in the immunosuppressed host is given in Table 27.1. Although fungi and other relatively unusual types of organisms are commonly thought to be the major causes of infectious infiltrates in patients receiving treatment for malignancy, bacterial pneumonia is still the most frequent problem in this setting. Neutropenia is an important predisposing factor for bacterial pneumonias, which frequently are due to Gram-negative rods or

Staphylococcus.

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