Evaluation of the child with frequent respiratory tract infections

ABSTRACT

Frequent respiratory tract infections (RTIs) in children represent a significant clinical challenge. While the majority of these children have identifiable benign explanations, such as maturing immune system or increased environmental exposure (e.g., attending daycare or having school-age siblings), a small subset suffers from serious immune deficiency (ID). Inborn errors of immunity (IEI) – historically referred to as primary immunodeficiencies (PID) – comprise a growing list of > 550 monogenic disorders. Delayed diagnosis of IEI remains a major problem, leading to significant morbidity and mortality. This review provides a practical approach for clinical evaluation and screening laboratory tests of children with frequent or unusual RTIs. A skillful medical history-taking and a comprehensive physical examination are of utmost importance in identifying valuable clues for suspicion of ID and sometimes a definite recognition of the disorder. Laboratory evaluation is essential to delineate the specific immune defect. The value of a routine complete blood count (CBC) with differential cannot be over-emphasized in discovering any cytopenia. Evaluation of the main components of the immune system should be in a systematic way, starting with screening tests and proceeding for detailed testing of the most suspected immunity compartment. Molecular genetic testing greatly enhanced the arrival to a precise diagnosis. Early involvement of a clinical immunologist would markedly expedite the diagnostic process and the planning of appropriate management, including family counselling. Until the specific treatment is initiated, the child should be protected from exposure to infections, live vaccines, and transfusion of non-irradiated blood cells. Advances in diagnostic tests and therapeutic modalities led to marked improvement in early diagnosis and targeted therapies ranging from immunoglobulin replacement to hematopoietic stem cell transplantation (HSCT) and gene therapy.

IMPACT STATEMENT

This article provides a systematic approach to identification of immunodeficiencies in children with frequent or unusual RTIs. The impact of early diagnosis and instatement of targeted therapy would be marked reductions in morbidity and mortality in immunodeficient children.

Key words

Respiratory infections; pulmonary infections; evaluation of immunity; immunodeficiency; inborn errors of immunity; primary immune deficiencies.