Pulmonary Manifestations of Primary Immunodeficiency Disorders in Children

Abstract

Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of immune system are decreased, missing, or of non-appropriate function. These diseases affect the development, function, or morphology of the immune system. The group of PID comprises more than 200 different disorders and syndromes and the number of newly recognized and revealed deficiencies is still increasing. Their clinical presentation and complications depend on the type of defects and there is a great variability in the relationship between genotypes and phenotypes. A variation of clinical presentation across various age categories is also presented and children could widely differ from adult patients with PID. Respiratory symptoms and complications present a significant cause of morbidity and also mortality among patients suffering from different forms of PIDs and they are observed both in children and adults. They can affect primarily either upper airways (e.g., sinusitis and otitis media) or lower respiratory tract [e.g., pneumonia, bronchitis, bronchiectasis, and interstitial lung diseases (ILDs)]. The complications from lower respiratory tract are usually considered to be more important and also more specific for PIDs and they determinate patients’ prognosis. The spectrum of the causal pathogens usually demonstrates typical pattern characteristic for each PID category. The respiratory signs of PIDs can be divided into infectious (upper and lower respiratory tract infections and complications) and non-infectious (ILDs, bronchial abnormalities – especially bronchiectasis, malignancies, and benign lymphoproliferation). Early diagnosis and appropriate therapy can prevent or at least slow down the development and course of respiratory complications of PIDs.

Infectious and Noninfectious Pulmonary Complications in Patients With Primary Immunodeficiency Disorders

“…These complications comprise a wide range of infectious conditions (eg, bronchitis, pneumonia, empyema, and lung abscess) and noninfectious conditions (eg, hilar/mediastinal adenopathies, and obstructive and restrictive lung diseases) [46,47]. The development of noninfectious manifestations of the lower respiratory tract is usually multifactorial owing to immune dysregulation (eg, chronic inflammation, autoimmunity, and allergy), adverse effects of therapies, and malignancies [8]. Lower respiratory tract complications are examined in the following sections.…”

“…The spectrum of respiratory manifestations is extremely wide, including acute and chronic infections (eg, recurrent, severe, persistent infections affecting various locations, and opportunistic or unusual pathogens), immune dysregulation (eg, autoimmunity, allergy, and lymphoproliferative disorders), structural abnormalities, and malignancies. As survival from infection improves (mortality from PID is still 30%-45% worldwide), noninfectious pulmonary complications are more frequently observed among patients with PIDs [8,9]. Standard management of the respiratory complications of PID is complemented by more specific therapeutic modalities, including surgery (otitis, sinusitis, adenoiditis, and lung infection), lung transplantation, and symptomatic therapies (anti-inflammatory drugs, mucolytics, bronchodilators, and inhalers).…”

Sinopulmonary Complications in Subjects With Primary Immunodeficiency

“…As expected, infections were the most common sinopulmonary manifestations in our cohort, which is consistent with previous reports. 29 In a previous study, 14% of the subjects who presented with recurrent pneumonia were found to have an underlying immune disorder. 30 Because respiratory infections are common in general, physicians should be alerted about the proper indications to work up patients for the possibility of primary immunodeficiency disorders.…”

“…As observed in our cohort, the pathogens that cause respiratory infectious complications in primary immunodeficiency disorder display a typical spectrum according to the immune defect. 29 This observation should aid in the diagnostic approach in an attempt to identify a particular type of primary immunodeficiency disorder. For example, patients with combined immunodeficiencies are prone to develop respiratory infections caused by a wide range of bacteria, fungi, and viruses, whereas patients with predominantly antibody deficiencies are at risk of developing bacterial respiratory infections.…”

Surveillance of Primary Immunodeficiency Disorders in Mofid Children's Hospital: A 10-year retrospective experience

“…Clearly, these diseases are not as rare as originally suspected. The spectrum of PID disorders has greatly widened in the past few decades, with more than 200 different disorders or syndromes, affecting the immune system development, function, or morphology (1,2). It is well accepted that clinical presentations of PID disorders are highly variable and include inflammatory, autoimmune, allergic, and lymphoproliferative symptoms, as well as susceptibility to recurrent infections, which is the hallmark of these disorders (3,4).…”