Definition

Chronic rhinosinusitis (CRS) in children is defined as an inflammation of the nose and the paranasal sinuses characterized by two or more symptoms, including either nasal blockage, obstruction, congestion or nasal discharge (anterior/posterior nasal drip) and cough or facial pain or pressure. The diagnosis also requires objective signs of disease documented by endoscopy and/or computed tomography (CT) scan. In general, CRS refers to symptoms that last 12 weeks or longer without symptom-free periods.

Prevalence

Although CRS is a commonly encountered problem, the exact prevalence in children is difficult to determine. Many studies that address prevalence have been performed in children who also have nonspecific upper respiratory complaints. In one such study, CT scans were obtained in 196 children 3 to 14 years of age presenting with chronic rhinorrhea, nasal congestion, and cough. Maxillary involvement was noted in 63%, ethmoid involvement in 58%, and sphenoidal sinus involvement in 29% of the children of the youngest age groups, and the incidence of abnormalities decreased in the 13- to 14-year-old age group. In a prospective study, all new patients (ages 2 to 18 years) who presented to two allergy practices with upper respiratory tract symptoms for at least 3 months were investigated with a CT scan. In 91 eligible patients, 63% had CRS with clinical signs and positive CT findings, and 36% had no sinus disease. Age was the single most important risk factor associated with chronic sinusitis, and 73% of 2- to 6-year-olds, and 74% of 6- to 10-year-olds had sinus CT abnormalities as opposed to the low incidence of only 38% detected in children over 10 years of age. Evidence suggests that children with a family history of atopy or asthma who attend day care in the first year of life have 2.2 times higher odds of having physician-diagnosed sinusitis than children who do not attend day care.

Clinical Symptoms

The four most common clinical symptoms are cough, rhinorrhea, nasal congestion, and postnasal drip, with a slightly higher predominance of chronic cough. Tatli and colleagues found that 66% of children who undergo evaluation for chronic cough had CT scan abnormalities in the paranasal sinuses. The clinical diagnosis of CRS in children is challenging, related to the overlap of symptoms with other common childhood nasal diseases such as viral upper respiratory tract infections, adenoid hypertrophy/adenoiditis, and allergic rhinitis. Furthermore, the history is limited to the subjective evaluation by the child’s parents, and some younger children may not tolerate nasal endoscopy. It is often very difficult to differentiate CRS from adenoid hypertrophy/adenoiditis in young children. A thorough history of the timing of symptoms is critical to attempt to define the category of disease that best applies to each patient. A very common clinical scenario in children who present to the office is that of CRS with upper respiratory tract infection–induced acute exacerbations.

Quality of Life

In a study of children with chronic and recurrent rhinosinusitis who failed medical treatment and required surgical intervention, Cunningham and colleagues showed significant impairment of generic quality-of-life (QOL) measures. In these children, QOL scores were significantly lower than those of children with other common chronic diseases such as asthma, attention-deficit/hyperactivity disorder, juvenile rheumatoid arthritis, and epilepsy.

The SN-5 survey is a disease-specific tool completed by parents to reflect the previous 4 weeks. It consists of five domains that include sinus infection, nasal obstruction, allergy symptoms, medication use, emotional distress, and activity limitations. The survey correlates with CT scan scores in patients with CRS and was validated as a measure of change over time in sinonasal symptoms. However, limited evidence of improvement of SN-5 scores was noted in patients with CRS after surgical intervention.

Anatomic Factors

As in adults, the critical anatomic structure in rhinosinusitis is believed to be the ostiomeatal complex, which is entirely present, although not at full size, in newborns. In a study that evaluated CT scans of 65 children with persistent symptoms of CRS, the most common abnormality was an agger nasi cell, followed by concha bullosa, paradoxic middle turbinate, and a Haller cell. However, the authors found no significant correlation between the anatomic abnormalities and the extent of sinusitis on imaging. It is difficult to assess the importance of anatomic abnormalities in pediatric CRS because no studies include a determination of the prevalence of these abnormalities in a control group. Current evidence would suggest that despite the common occurrence of these anatomic factors, they do not seem to correlate with the degree and existence of CRS.

Bacteriology

The pathogens involved in CRS are difficult to identify because of low bacterial concentration rates and inconsistent data. Furthermore, most cultures are obtained at the time of surgery after patients have been treated with antibiotic therapy. In such studies, common organisms include alpha-hemolytic streptococci, Staphylococcus aureus , Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis . Anaerobic organisms are infrequently identified.

Biofilms

Biofilms are complex aggregations of bacteria distinguished by a protective and adhesive matrix. It is hypothesized that biofilms may provide a reservoir for bacteria and may be responsible for the resistance to antibiotics seen in patients with CRS. Sanclement and colleagues demonstrated the presence of biofilms in 80% of sinus surgical specimens obtained from a mixed adult/pediatric population. More research is needed to clearly characterize the contribution of biofilms to the pathophysiology of CRS in children.

Role of Adenoids

The adenoids are in close proximity to the paranasal sinuses, and adenoidectomy is effective in resolving symptoms in some children with CRS. Zuliani and colleagues found that a large percentage (88% to 99%) of the mucosal surface area of adenoidectomy specimens from children with CRS was covered with a dense biofilm compared with a much more modest percentage (0% to 6.5%) of the specimen surface area in the adenoids of patients with sleep apnea. This work provides a potential explanation for the improvement seen with adenoidectomy in antibiotic-resistant CRS. Another study suggested that hypertrophied adenoids share similar bacteriology with the middle meatuses of children with chronic or recurrent sinusitis, such that adenoid core culture had a positive predictive value in forecasting middle meatal cultures. Furthermore, the isolation rates of bacteria from adenoids of children increased proportionately to sinusitis severity on radiographs. In contrast, in children with nasal discharge who underwent adenoidectomy, no correlation was found between the size of the adenoids and the severity of disease on CT. This lack of correlation suggests that the nasal discharge could be due to adenoiditis alone, or, alternatively, the contribution of the adenoids to CRS may relate more to their bacterial reservoir than to their size. However, studies are small, and they evaluate the adenoids after surgical removal. In summary, current evidence to support the role of adenoids in CRS is emerging but does not really shed light on the relative contribution of adenoiditis proper versus CRS in chronic nasal symptomatology in children.

Cellular Studies

Studies of the cellular response in pediatric CRS in older children indicate that eosinophils and CD4-positive lymphocytes play a significant role in tissue inflammation. In similar studies performed in younger children, Chan and colleagues showed that pediatric maxillary sinus mucosa had more neutrophils and significantly more lymphocytes than adult mucosa but had fewer eosinophils and major basic protein–positive cells, with less epithelial disruption and less basement membrane thickening. These authors also showed higher numbers of CD8-positive cells, neutrophils, macrophages, B lymphocytes, and plasma cells in younger children with CRS compared with adults. The differences in eosinophil versus neutrophil predominance in the specimens studied above probably relate to the age group of the children studied (eosinophil predominance in the older children and neutrophil predominance in the younger ones) and to the tissues used for comparison (none in the first study and adult tissues in the second).

Allergic Rhinitis

Allergic rhinitis commonly coexists with CRS in children. In a mixed adult and pediatric population with CRS refractory to medical treatment on whom a radioallergosorbent (RAST) test as well as a CT scan were available, 40% of the patients were atopic, and patients with a positive RAST test had a significantly higher CT score compared with the patients who had negative test results. In a study in Thailand of 100 children with a clinical diagnosis of sinusitis and abnormal plain radiographs, a positive skin test to common aeroallergens was reported in 53% of the patients, which suggests a correlation between allergic rhinitis and CRS. In contrast, a study from Belgium evaluated CT scans from allergic and nonallergic children and noted the presence of sinus opacification in 61% and 64% of allergic and nonallergic children, respectively, which suggests a lack of an important role of allergy in sinus CT abnormalities. A similarly negative study in children with chronic respiratory symptoms found no correlation between atopic status and sinus abnormality on CT; the prevalence of sinus disease was similar in the atopic patients (63%) versus the nonatopics (75%). A study of 351 Italian children showed no significant difference in the incidence of positive allergy tests, with 30% positive in the CRS children and 32% positive in the general population. The incidence of positive allergy testing was significantly higher in children older than 6 years compared with those younger than 3 years. Thus the causal relationship between allergies and CRS in children remains controversial. When symptoms of allergic rhinitis are prominent, allergy testing should be considered in the older child.

Asthma

Asthma is another disease that is commonly associated with CRS in the pediatric age group. Rachelefsky and colleagues reported on treatment outcomes in 48 nonrandomized children with moderate to severe asthma and comorbid CRS. After pharmacologic or surgical intervention for sinusitis, 80% of these children were able to discontinue asthma medications. Furthermore, asthma recurred when sinusitis subsequently relapsed. In another study, Tosca and colleagues identified 18 children 5 to 12 years of age who had poorly controlled asthma and comorbid CRS. The patients were treated for 14 days with antibiotics and intranasal and systemic steroids and were evaluated at baseline, after treatment, and 1 month later. In addition to improvement in their nasal symptoms, patients had a significant improvement in spirometry, wheezing, and inflammatory markers in nasal lavage specimens. These and other studies support the concept that clinical control of CRS may be important in optimizing the control of difficult-to-treat asthma. However, the limitations of most available studies include the lack of good controls or randomization to different treatment modalities; therefore, the relationship between CRS and asthma in children remains largely descriptive.

Gastroesophageal Reflux Disease

Gastroesophageal reflux disease (GERD) has also been associated with rhinosinusitis in several studies. Phipps and colleagues conducted a prospective study of pediatric patients with CRS and found that 63% of children with CRS had GERD documented by pH probe. In addition, 79% experienced improvement in rhinosinusitis symptoms after medical treatment of GERD. In a large case-control study that included 1980 children aged 2 to 18 years with GERD and 7920 controls, a diagnosis of sinusitis was significantly more likely in the children with GERD (4.19%) compared with the control group (1.35%). A retrospective study that lacked a placebo control showed that treatment for GERD in patients with CRS allowed many patients to improve and avoid surgery. Routine antireflux treatment of children with CRS is not warranted because additional controlled studies are required to confirm and validate this association.

Immunodeficiency

Several small studies have demonstrated various abnormalities in humoral immune function, including low immunoglobulin G (IgG) subclasses, low IgA, and poor response to pneumococcal antigens in varying proportions of the patients. In an open-label pilot study, six patients with CRS refractory to medical management were treated with intravenous (IV) IgG for 1 year, which resulted in a decrease in days of antibiotic use from 183 to 84 days and a reduction in episodes of sinusitis from nine to four per year. CT scans also showed significant improvement. It therefore seems prudent to evaluate immune function in the child with chronic/recurrent rhinosinusitis with an immunoglobulin quantitation and titers to tetanus and diphtheria in addition to pneumococcal titers. If responses are abnormal, a repeat set of titers after pneumococcal vaccination is appropriate.

Primary Ciliary Dyskinesia

The most common cause of ciliary dysfunction is primary ciliary dyskinesia (PCD), an autosomal-recessive disorder that involves dysfunction of cilia, which affects 1 in 15,000 individuals. Approximately 50% of children with PCD also have Kartagener syndrome (situs inversus, bronchiectasis, and CRS). The diagnosis of PCD should be suspected in a child with atypical asthma, bronchiectasis, chronic wet cough and mucus production, rhinosinusitis, and chronic and severe otitis media. Patients with suspected PCD may be screened by nasal nitric oxide levels, which are lower in PCD patients than in controls, or by in vivo tests such as impaired nasal mucociliary transport of saccharin. Specific diagnosis may require evaluation at a specialized center that can perform examination of cilia in mucosal biopsies by light and electron microscopy. Common sites for mucosal biopsy include the trachea (carina) or nasal mucosa; although it requires a bronchoscopy, the carina may be preferable because chronic inflammation in the nose may interfere with proper interpretation of ciliary morphology.

Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal-recessive disease caused by mutations in the CFTR gene. The incidence of CF is approximately 1 in 3500 newborns. Disruption in cyclic adenosine monophosphate–mediated chloride secretion in epithelial cells and exocrine glands leads to increased viscosity of secretions that results in bronchiectasis, pancreatic insufficiency, CRS, and nasal polyposis. CF is one of the few causes of nasal polyposis in children; polyps occur in 7% to 50% of patients, and the prevalence of chronic sinusitis is very high.