Disease-specific studies focused on infection risk in primary antibody deficiencies are needed to define strategies for controlling respiratory infections. Little information is available on the rate of airway bacterial carriage and its consequence. In hypogammaglobulinemias, Despite IgG replacement, recurrent respiratory infections are common in PAD possibly leading to chronic lung damage and poor quality of life. Thus, patients are often prescribed antibiotics and/or long-term antimicrobial prophylactic regimens. However, antibiotics influence antimicrobial resistance among airway microbiota. In a recent meta-analysis on patients with chronic lung diseases, 30% of S. pneumoniae showed resistance to macrolides.
In this observational longitudinal study, we will investigate the rate of nasopharyngeal and oropharyngeal mucosal carriage detected by cultural methods and Real-time-PCR (RT-PCR), the antimicrobial susceptibility patterns and the antibiotic usage in 300 adult patients with Common Variable Immunodeficiency (http://esid.org/Working-Parties/Registry/Diagnosis-criteria). Additionally, we will verify whether colonization would be associated with risk for respiratory infections. Rate of respiratory infections, clinical data and days of antibiotic usage in the six months prior to swabs collection will be recorded. Sample collection and identification of bacteria will be performed according to the WHO standard procedures by cultural and molecular methods on swabs collected on the same day. For both bacterial species, minimum inhibitory concentrations of antimicrobial agents will be determined by the interpretative criteria based on EUCAST breakpoints (http://www.eucast.org/clinical breakpoints/). Diversity and type of airways colonizing microbiota will be performed by amplification of the V3-V4 16S rRNA gene region. After swabs collection, respiratory infections will be recorded for additional 6 months.
Despite IgG replacement treatment, in PAD recurrent respiratory tract infections, remain of great concern, resulting in progressive bronchiectasis and in respiratory function impairment. Data the rate on airways bacterial colonization in PAD and on its consequence on the recurrence of respiratory tract infections are lacking and might provide a good model to identify protective mechanisms. It is possible to hypothesize that low IgM and low IgA mucosal and serum levels might be a major risk factors for bacterial colonization. In particular, the study of the role of mucosal IgA seems to be relevant since IgA comprises over 90% of the antibody in the upper and lower respiratory, block adherence to the host respiratory epithelial cells and enhance local agglutination of the bacteria, especially at the beginning of colonization. To neutralize IgA, many pathogenic bacteria including S. pneumoniae and H. influenzae has evolved virulence factors, such as IgA1 proteases. The actual impossibility to replace IgA and IgM at mucosal level in PAD implied the need to consider additional therapeutic interventions , such as the use of antibiotic treatment or prophylaxis. However, a major concern related to the use of therapy or prophylaxis with antibiotics is that such use might exert selective pressure on airway microbiota facilitating the emergence of antibiotic resistance. To our knowledge, no data on antibiotic resistance of bacteria colonizing PAD patients were available in the literature. Previous studies investigating bacterial colonization in healthy subjects found a wide variation in carriage rate depending mainly on geographic areas, detection methods (culture vs molecular methods), sampling sites, age groups and health state of subjects. Most of studies actually regard children, who are frequently colonized. In Italy, relatively high colonization rates were observed in children aged