Complications due to acute rhinosinusitis in children

Abstract: Background There is a lack of population-based studies of complications to acute rhinosinusitis in children. Previous studies have demonstrated a possible effect of the conjugate pneumococcal vaccine (PCV) on hospital admissions and bacteriology in acute rhinosinusitis. There is a lack of prospective studies that investigate the possible association between complications to acute rhinosinusitis in children and: specific respiratory viruses, allergy sensitization and immunoglobulin levels in blood. The aim was to describe complications due to acute rhinosinusitis in children, 0-18 years old, in Stockholm, Sweden, including clinical presentation, incidence rates, results of bacterial cultures, and analyze factors that could have an effect on this rare disease – pneumococcal conjugate vaccine, concomitant virus infection, IgE-sensitization to airborne allergies and immunoglobulin levels. Methods All papers in this thesis included children hospitalized due to acute rhinosinusitis (ARS) and related complications in Stockholm Region. Paper I-III were population-based, observational cohort studies with retrospectively collected data. Paper I included children up to five years old, before the introduction of PCV, study period 2003-2007. Paper II included the same age but after PCV introduction, study period 2008-2016, and included a comparative data analysis with paper I. Paper III included children from five to 18 years old, study period 2003-2016. In paper I-III, hospital admissions of children with a discharge diagnosis of rhinosinusitis and related complications were included and reviewed. Paper IV was a prospective cohort study of children up to 18 years old. The study period was april 2017 to april 2020. Inclusion criteria was acute bacterial rhinosinusitis and hospitalization. Data was gathered including: bacterial cultures from the nasopharynx, the nasal middle meatus, and bacterial cultures and broad-range 16s rDNA PCR from the surgical site; viral nasopharyngeal PCR; allergy sensitization IgE test; and immunoglobulins in blood. In paper I-IV, the CT and MRI images were reviewed by a specialist in radiology. Incidence was expressed as cases per 100 000 children in studied age groups per year. Results There were 213 admissions (203 individuals) in paper I, 217 admissions (215 individuals) in paper II, 310 admissions (304 individuals) in paper III and 55 cases in paper IV. Comparing paper I and II, the incidence of hospital admission due to acute rhinosinusitis and related complications in children up to five years old decreased from 43.8 to 18.8 children per 100 000 per year, after the introduction of PCV. A CT/MRI verified postseptal orbital complication was found in 3.3% of admissions in paper I (mean incidence 1.51) and in 13.4% in paper II (mean incidence 2.54). Surgery increased from 0.5% of the admissions in paper I (mean incidence 0.22) to 4.1% in paper II (mean incidence 0.79). In paper III, the incidence of hospital admission due to ARS and related complications in children from five to 18 years old was 7.8 per 100 000 per year. A CT/MRI verified severe complication (postseptal orbital, intracranial or osseous) was found in 34%, representing an incidence of 2.6 per 100 000 per year. Surgery was performed in 17% of admissions (mean incidence 1.3). In paper I-III, between 80-96% of admissions had preseptal cellulitis. In paper I-II, males had a higher incidence of admission and postseptal complication compared to females. In paper III, males had a higher incidence of admission, all type of complications and surgery, compared to females. S. pneumoniae was the most common bacteria found in nasal and blood cultures in paper I, but was not dominant in the nasal or 10 blood cultures and absent in the surgical cultures in paper II. H. influenzae and S. pyogenes dominated in the nasal cultures in paper III, S. milleri was the dominating bacteria in surgical cultures (33%), and S. pyogenes dominated in blood cultures. In paper IV, cultures from the middle meatus were positive for bacterial growth and displayed a wider range of bacteria compared to the nasopharyngeal cultures. There was a match of at least one type of bacteria in the MM and NPH culture in 36% of the cases. M. catarrhalis was possibly associated with a lower number of days with intravenous antibiotics (-1.3 p=0.055), H. influenzae and S. pneumoniae negatively associated with max CRP (-38.9 p=0.028 and -45.5 p = 0.023), and S. pyogenes positively associated with max CRP (57.5 p=0.007). S. milleri was found in the surgical culture in 58% of the cases that has surgery. The nasal cultures were negative in 58% of the cases that had surgery. In the surgical cultures, 16S rDNA PCR resulted in a higher number of positive results in comparison to the traditional swab and tissue cultures. The viral nasopharyngeal PCR was positive in 53% of the cohort in paper IV, and influenza A was most common. Positive viral PCR was associated with a lower grade of complication (-1.3, p=0.028) and CRP max (-36.2, p=0.05). Influenza virus was possibly associated with a lower grade of complication (-2.2, p=0.055). An association was found between S. pyogenes and influenza A/B positive cases (1.5 p=0.040). The cases with a positive viral PCR and total number of cases followed the same monthly distribution during the year. The allergy sensitization test was positive in 29% of the cohort and in 50% of the cases that had surgery, and possibly associated with a higher number of days with IV antibiotics (1.2, p=0.052). No cases had decreased immunoglobulins. Conclusions The incidence of complications to acute rhinosinusitis in children in the population is low. Children from five years and older that are hospitalized due to acute rhinosinusitis have a substantial risk of developing severe complications. There is a wide range of complications to rhinosinusitis, and many aspects needs to be considered in the caretaking of children with complications. The introduction of PCV, presence of certain airborne viruses and sensitization to airb