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Lung infectious disease is an important cause of morbidity and mortality in patients with primary immunodeficiencies and other conditions that alter immunologic mechanisms against microbial invasion. Lung infectious diseases occurring in patients with congenital immunodeficiency and patients on treatment with biologic anti-inflammatory compounds are discussed. Understanding of the complex relationships between the immune system and microbes is of paramount importance for timely diagnosis and successful treatment of lung infectious diseases in this group of immunocompromised hosts.In the past, only a minority of children with severe primary immunodeficiency survived beyond childhood and these disorders were within the scope of the pediatrician. As modern prophylaxis and treatment strategies have been implemented, these patients will now survive into adulthood. Nowadays, therapy with new biologic compounds – tumor necrosis factor (TNF) blockers and anti-CD20 drugs – that disrupt antimicrobial surveillance and the control of intracellular microorganisms such as mycobacteria, fungi and viruses has been associated with the emergence of a new population at risk for the development of severe pulmonary and disseminated infectious diseases.A wide array of bacteria, viruses, fungi and protozoa may cause severe pulmonary infectious diseases in patients with primary immunodeficiency and patients on treatment with anti-TNF and anti-CD20 drugs. Knowledge of the association of certain microbial agents with specific immune disturbances is of great clinical interest.