Salivary Polyreactive Antibodies and <i>Haemophilus influenzae</i> Are Associated With Respiratory Infection Severity in Young Children With Recurrent Respiratory Infections

To determine whether any laboratory studies may predict a predisposition for recurrent respiratory tract infections (rRTis).The cohort included 100 children younger than 10 years with RTls who were referred for immunological screening. The comparison group was family.rRTis were determined based on the age of the patient. rRTis were defined as at least 11 upper rRTis/y for age up to 2 years, 28 upper rRTis 2 to 5 years, 26 for 5 to 8 years, or at least 2 pneumonia diagnoses in a year or 3 in a lifetime. In the study cohort, a saliva and serum sample were obtained at baseline. In the control group, serum and saliva samples were collected before and 4 weeks after receiving the influenza vaccine to detect any changes in antibody levels. In the study cohort, saliva was collected at baseline and nasopharyngeal swabs were collected in the first month. The swabs were analyzed for microbiota 165 RNA sequencing and detection of 12 respiratory viruses by quantitative PCR (qPCR) and Haemophilus subtyping by qPCR. For children with rRTis, immunologic screening was done.A high proportion of salivary immunoglobulin A (IgA) polyreactive antibodies were found in saliva compared with serum in patients with rRTis. Serum antibody deficiencies were not associated with increased rRTi severity or viral burden. Decreased levels of polyreactive IgA and IgG in saliva were associated with rRTi severity. Also, Haemophilus influenzae abundance is associated with RTI symptom burden. The symptoms were monitored daily via a cell phone app.The findings support that serum antibody levels are not associated with disease burden. The study underscores that the role of H influenzae in the respiratory microbiota is associated with reduced levels of polyreactive IgA and increased RTis. This supports the need to analyze the mucosal immune system to enhance the understanding of rRTis in children.Although these data help us better understand the immune response of mixed viral and bacterial infections, we are still left with currently not having any readily available diagnostics tests that will allow identification of these abnormalities and a method of treatment that will allow intervention to halt recurrent lower respiratory tract infections.