The lung is a common site of infection in patients with cancer. The spectrum of pulmonary infection depends on the underlying immunologic deficit or deficits. In neutropenic patients, gram-negative bacterial infections predominate early, whereas fungal infections (Aspergillus, Zygomycetes, Fusarium species) are common if neutropenia persists. In patients with impaired cellular immunity, viral infections (cytomegalovirus, other herpes viruses) predominate and may coexist with bacterial (Legionella, Nocardia), mycobacterial, and fungal (Aspergillus, Histoplasma, etc.) infections. Pneumocystis carinii pneumonia is also common in this setting. Infections caused by Streptococcus pneumoniae and Haemophilus influenzae are the primary bacterial infections encountered in patients with impaired humoral immunity. In patients with primary or metastatic pulmonary neoplasms, postobstructive pneumonitis, lung abscess, and occasionally empyema of mixed bacterial etiology (Staphylococcus species, gram-negative bacilli, anaerobes) are frequent. Patients with brain tumors and head and neck cancer develop aspiration pneumonitis, which is usually caused by organisms living in the oropharynx and upper airways. Several immunologic deficits might be present in the same patient, making such a patient susceptible to a wide variety of opportunistic pathogens.

Respiratory infections during chemotherapy-induced aplasia.Rev Mal Respir. 2001 Apr;18(2):125-35.

Damage to local and systemic host defenses of the lung makes the immunocompromised patient vulnerable to inhaled microorganisms. When a pulmonary infiltrate occurs, the array of possibilities is very large including conventional and opportunistic agents. The type of underlying disease and its associated immunodeficiency allow a high degree of accurate pathogen prediction. Neutropenia is associated with Gram-negative bacilli pneumonia. Prolonged neutropenia increases the risk of invasive aspergillosis and other unusual mycotic agents. Cellular immunodeficiency is associated with intracellular microorganisms including Mycobacteria spp., Nocardia spp., Legionella spp., Rhodococcus equi, cytomegalovirus, Strongyloides stercoralis, Toxoplasma gondii, Histoplasma capsulatum, Coccidioides spp., Cryptococcus neoformans and Pneumocystis carinii, parasites such as Toxoplasma gondii and Strongyloides stercoralis, and virus such as cytomegalovirus, Herpes simplex or zoster, adenovirus, respiratory syncitial virus and measles. Humoral immunodeficiency predisposes to infection with encapsulated pathogens such as S. pneumoniae and Haemophilus influenzae. Chest computerized tomography scan and bronchoalveolar lavage are essential procedures for diagnosis. However, despite continuous progress in diagnostic methods, the specific etiology remains often unknown. Successful treatment depends on the type of pathogen, status of host defences and early adequate choice of antibiotic. Enhancement of host defences with growth factors and cytokines may decrease the incidence and improve the final outcome of respiratory infections in the immunocompromised host.

Pulmonary defense mechanisms against opportunistic fungal pathogens. Immunol Ser. 1989;47:243-71.

Though of critical importance, nonimmune host defense mechanisms against aspergillosis and mucormycosis are not completely understood. Prevention of these infections presumably requires control of either spore germination and/or hyphal growth by the host. The data suggest that the host provides an important barrier to infection by control of spore or conidia germination, the critical step involving conversion of the fungus to its tissue-invasive form. The mechanisms of host defense against A. fumigatus are not strictly dependent on inhibition of conidia germination. Rather, pulmonary defense against Aspergillus appears to depend to a greater degree on early killing of fungal conidia by alveolar macrophages. In contrast, prevention of mucormycosis appears to require inhibition of fungal spore germination by the bronchoalveolar macrophage, thereby preventing conversion of the fungus to its hyphal form, although resident bronchoalveolar macrophages are unable to kill R. oryzae spores. Thus, host pulmonary defenses to Rhizopus and Aspergillus vary, even in normal animals. The tissue-invasive hyphal forms of the fungi which cause aspergillosis and mucormycosis are too large to be ingested by phagocytic cells. Although macrophages and monocytes can damage hyphae, the bulk of this role appears to fall upon the neutrophil. However, antihyphal mechanisms of neutrophils may not necessarily be identical for all types of hyphae. Moreover, interactions of several potential oxidative and nonoxidative antihyphal mechanisms may define the host's ability to limit fungal infections. In individuals where concentrations of oxidative or nonoxidative substances are limiting or suboptimal, interactions of mechanisms may be required for antihyphal activity, and studies of these interactions are important to gain better knowledge of the defense mechanisms against opportunistic mycoses in the intact host. In summary, at least two distinct lines of defense against Aspergillus and Rhizopus are known in the normal host. Alveolar macrophages kill Aspergillus conidia and prevent germination of Rhizopus spores. The neutrophil damages the hyphal form of Aspergillus and Rhizopus. Thus, neutrophils and monocytes or macrophages act as distinct components of host defenses against aspergillosis and mucormycosis, and they may also operate by different mechanisms. Both invasion of tissue and environmental contact with aspergilli and the Mucorales induce the production of antibodies to these organisms. However, any definite role of antibodies or B cell-dependent immunity in effective host defense against initial invasion is still in doubt. It appears that the natural resistance of the host to Aspergillus depends primarily upon nonimmune factors. However, if these factors are breached, it remains possible that humoral immunity may play a role in host defense by limiting hyphal growth, perhaps in conjunction with phagocytic cells. The importance of cell-mediated immunity in resistance to aspergillosis and mucormycosis is not yet understood. It appears that the initial susceptibility to lethal infection is substantially T cell independent.

Host defense impairments that may lead to respiratory infections.
Clin Chest Med. 1987 Sep;8(3):339-58.

Host defense mechanisms spaced along the respiratory tree and in the alveolar spaces effectively remove or contend with micro-organisms that enter the airways, so serious lung infections occur rarely in healthy people. Special circumstances, such as virgin exposure to a virulent microbe or a large innoculum of a pathogen, can result in illness, but usually routine surveillance host defenses are protective and suffice to keep colonizing airway flora in check. When pneumonia develops or recurrent sinopulmonary infection exists, however, some element of the normal defense apparatus may have failed or is inadequate. This review highlights several components of the apparatus, that is immunoglobulins IgG and IgA and the interaction of alveolar macrophages and lymphocytes, and examines deficiencies in their function that may result in infection. Along the conducting airways, poor mucociliary clearance and/or deficiencies in certain IgG subclass antibodies or destruction of IgA may predispose to sinopulmonary infections; these may be a manifestation of a hereditary disease. In pneumonia the alveolar macrophage is positioned as the central cell which must respond in several directions. This scavenger phagocyte first intercepts the microbe and either can kill or contain it or must call in some other phagocytic cell or inflammatory mediator(s) for assistance. Opsonic antibodies (IgG) and other nonimmune opsonins (complement and surfactant or fibronectin fragments) facilitate phagocytosis, but an absence of antibody may permit infection to develop with encapsulated bacteria (pneumococcus). Insufficient bone marrow reserves of PMNs or a paucity of chemotactic factors to attract them into the alveoli is a situation that may permit gram-negative bacilli and fungal organisms to flourish. Inability of immune T-lymphocytes to energize macrophages, through soluble cellular mediators that provide cell-mediated immunity and activation, makes containment of certain intracellular microbes impossible for these phagocytes (Legionella or mycobacteria). Likewise, concomitant infection of macrophages with viruses (human immunodeficiency virus, and cytomegalovirus or herpes viruses) plus an excessive T-lymphocyte suppressor cell influence may make P. carinii and common bacterial and fungal organisms difficult to contain in the lungs of AIDS patients. Consideration about what the lung host deficiency might be can make therapy more specific through immunization to develop special antibodies, replacement of certain immunoglobulins (IgG subclasses), or selective administration of cell mediators (gamma-interferon or interleukins).

Lung defense against infection. J Pediatr. 1986 May;108(5 Pt 2):813-6

The human lung has an exquisitely effective and complex defense against infections. Mucus prevents attachment of bacteria to the epithelium, and those bacteria that cannot cross the mucus are cleared by exhalation or by the mucus-ciliary escalator. Alveolar macrophages dispatch microbes that reach the peripheral barriers of the lung. The pulmonary phagocytic system immobilizes, kills, and walls off invading bacteria. The phagocytic system, developed in bone marrow, includes alveolar macrophages, granulocytes, and monocytes. The phagocytic system is amplified by humoral factors, including inflammatory mediators, acute-phase reactants, and opsonins that allow rapid engulfment and killing of microbes. Highly mobile polymorphonuclear granulocytes reinforce the macrophages when invading organisms reach tissue. Sterility of the lower respiratory tract in the normal host is evidence that the defense systems of the lung are highly effective and potently bactericidal. The oxidative and nonoxidative microbicidal mechanisms of alveolar macrophages and granulocytes are lethal for most ordinary microbes. However, certain pathogens have means of preventing phagocytosis, and obligate intracellular species have evolved mechanisms of intracellular survival. Successful biologic detente between microbe and host is the usual situation in the normal human lung, but the relationship is unfortunately short-lived in patients with cystic fibrosis. Mucus is not an adequate barrier in these patients. Bacterial pathogens colonize respiratory tissue and, as a consequence, compromise lung function. Better understanding of local defenses in normal human lungs and of the defects in lung defenses in patients with cystic fibrosis should lead to methods that will provide these patients with successful defense against invading microbes.

Respiratory infections may reflect deficiencies in host defense mechanisms. Dis Mon. 1985 Feb;31(2):1-98.

Serious respiratory tract infections are rare in the healthy individual and most of the nuisance morbidity that occurs results from nasopharyngeal viral infections that many people get once or twice a year. The economic impact from these upper respiratory tract infections is appreciable, however, in terms of absenteeism from school or work, but unfortunately there is little that can be done to ward them off in a practical way. Pneumonia is an infrequent lifetime experience for most non-smoking adults and when it occurs, unusual circumstances may pertain--a particularly virulent microorganism is in circulation, or perhaps one has been exposed to a newly recognized germ, such as has occurred with Legionella species in the past 8 years or so. What protects us the great majority of the time is a very effective network of respiratory tract host defenses. These include many mechanical and anatomical barrier mechanisms concentrated in nose and throat; mucociliary clearance, coughing and mucosal immunoglobulins in the conducting airways and in the air-exchange region of the alveolar structures, phagocytes, opsonins, complement, surfactant and many other factors combine to clear infectious agents. The ability to mount an inflammatory response in the alveoli may represent the maximal and ultimate expression of local host defense. In some way these host defenses are combating constantly the influx of micro-organisms, usually inhaled or aspirated into the airways, that try to gain a foothold on the mucosal surface and colonize it. But many general changes in overall health such as debility, poor nutrition, metabolic derangements, bone marrow suppression and perhaps aging promote abnormal microbial colonization and undermine the body's defenses that try to cope with the situation. It is a dynamic struggle. The departure from normal respiratory health may not be obvious immediately to the patient or to the physician and repeated episodes of infection or persisting symptoms of cough, expectoration and sinus or ear infections may develop before serious assessment of the situation is taken and appropriate diagnosis gotten underway. Obvious explanations for respiratory infections may be apparent and, nowadays, side effects from antineoplastic chemotherapy or immunosuppressive therapy for a variety of diseases that create an immunocompromised host are common. In a few subjects, especially young adults who present with a cumulative history of frequent but mild infections in childhood and youth, a subtle deficiency in host defenses may exist and have been partially masked because of attentive pediatric medical care and prompt use of broad spectrum antibiotics.

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