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Original Studies

Low Prevalence of Severe Underlying Pathology in Children With Recurrent Respiratory Tract Infections

Peeters, Daphne MD*; Verhulst, Pieter MD; Vaessen-Verberne, Anja APH MD, PhD; van den Tweel, Xandra W. MD, PhD§; Noordzij, Jeroen G. MD, PhD; Driessen, Gertjan J.A. MD, PhD*,∥

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The Pediatric Infectious Disease Journal: November 2021 - Volume 40 - Issue 11 - p e424-e426
doi: 10.1097/INF.0000000000003256


Recurrent respiratory tract infections (RRTIs) including, ear, nose, throat (ENT) infections are very common in children. Approximately 10%–20% of children 0 to 10 years old suffer from RRTIs, leading to antibiotic treatment, ENT surgery or even hospitalization in the first years of life.1,2 Risk factors for respiratory infections are day-care attendance and parental smoking.3,4 However, sometimes RRTIs are the presenting symptom of an underlying disease. Previously reported prevalences are mainly studied in tertiary care hospitals or in children with predominantly lower respiratory tract infections.5–7 This poses a diagnostic challenge for the pediatrician in general pediatric practice who is consulted by otherwise healthy children with mainly upper RRTIs. Information is scarce regarding the prevalence of underlying disease in these children in nonacademic pediatric departments. In addition, evidence for the most optimal diagnostic strategy to detect underlying conditions is lacking.8 Current diagnostic protocols are mostly expert based, like the protocol for diagnosis of primary immunodeficiencies of the European Society for Immunodeficiencies.9

In this study, we report the clinical and diagnostic characteristics of children with RRTIs in nonacademic general pediatric practice. The aim of this study was to estimate the prevalence and severity of underlying conditions and to examine the diagnostic strategy that pediatricians were using to diagnose these conditions.


This retrospective observational cohort study examined children with complaints of RRTIs who visited a pediatric outpatient clinic of two large general nonacademic hospitals during a one-year period (July 2013 till July 2014). Screening for eligibility was performed based on the Diagnosis Treatment Combination codes, which are mainly registered for financial purposes. The electronic medical records of children with a respiratory/ENT Diagnosis Treatment Combination-code were screened. We enrolled all patients who were referred because of upper or lower RRTIs during this period or who had RRTIs as a new main symptom during follow-up care for other reasons. Children were excluded if they had a single episode or known medical history of underlying or complicating disease which could explain the high frequency of respiratory complaints. We collected clinical and diagnostic data from the electronic medical records. Failure to thrive, severe infection (other than pulmonary), or chronic diarrhea (>3 weeks) were considered to be alarm symptoms.7–10 IgA deficiency was defined as an IgA value below the age-specific reference range.9 If the patient visited the outpatient clinic more than once, we collected data of the first 5 follow-up visits up to 15 months following the first consultation.

Data was analyzed using IBM SPSS Statistics 24. Descriptive analyses were performed on baseline characteristics, clinical, and diagnostic data. To compare the diagnostic work-up of children with lower RTIs, alarming symptoms or exposure to smoke, a Man-Whitney U test, Kruskal Wallis test, or χ2 test were used where applicable. The database was coded using unique study identifier codes, which was guarded by the local investigator. Informed consent was waived by the local Medical Ethical Committee, because patients were not subjected to any extra procedures. This study was performed in accordance with the declaration of Helsinki.


Clinical Presentation

Of 1814 children who visited the outpatient clinic because of single or multiple episodes of respiratory symptoms, 208 suffered from RRTIs without a known underlying cause. The median age at first presentation was 2.2 years (see Table, Supplemental Digital Content 1; One hundred eighty-nine children suffered from upper RRTIs, 19 from lower RRTIs, and 10 from both. Alarm symptoms which might indicate a severe underlying disease were present in 30 of 208 children (14%): 15 of whom failed to thrive (7%), 4 had chronic diarrhea (2%), and 13 previously suffered from a systemic or severe infection (6%). Common risk factors for being susceptible to respiratory infections, such as passive smoking or frequency of attending day-care facilities, were often not recorded in the electronic medical records. In 57% of children the pediatrician reported information about passive smoking. One in 3 of these children had at least one smoking parent (see Table, Supplemental Digital Content 1;

Diagnostic Tests

In search of possible illnesses, medical professionals used different diagnostic strategies regarding the choice of the diagnostic test and its timing. In 62%, the pediatrician requested at least one diagnostic test. Forty-seven percent of pediatricians examined hemoglobin, 48% white blood cell count, and 42% white blood cell differentiation as a basic screening. Specific IgE was examined in 39% to examine sensibilisation for an allergen. Serum immunoglobulins and IgG subclasses were examined in 33% and 21%, respectively. For 7% of patients, specific immunologic tests were conducted, such as CH50 (classic complement pathway), AP50 (alternative complement pathway), or specific antibo dies to vaccination antigens. Chest radiographs were performed in 18%, but over one-third of these were performed before the first evaluation for RRTIs at the outpatient clinic. Three patients were examined using other diagnostic imaging such as high-resolution computed tomography (2 patients) and sinus radiograph (1 patient). Five patients were screened for CF (5 sweat tests and 1 genetic screening) and 4 for PCD (FeNO), but all with a negative result.

The presence or absence of alarm symptoms or passive smoking as a risk factor seemed not to trigger pediatrician's decision to perform specific diagnostic tests (see Figures, Supplemental Digital Content 2; and Supplemental Digital Content 3; Also, patients with alarm symptoms were not subjected to a higher number of different tests than other patients. However, more often diagnostics were performed in children with lower RRTIs diagnostics compared with children with upper RRTIs only (84% vs 60%). This difference was significant for chest radiographs, but not for blood screening, PCD or CF screening.

Final Diagnosis

In 64% of children, the pediatrician did not detect a specific illness to cause the high frequency of respiratory infections. These children received a descriptive diagnosis such as ‘age-related recurrent infections’, and the symptoms were explained by a high exposition to predominantly viral pathogens in combination with a ‘maturing immune system’.

Of the 74 patients who were diagnosed with a specific disorder, 55% (n=41) received a pulmonary diagnosis such as preschool wheezing or asthma. One patient was diagnosed with gastro-esophageal reflux with micro-aspiration (clinical diagnosis). Four percent had a partial IgA deficiency (n=3), and no severe primary immunodeficiencies were diagnosed. No children were diagnosed with new neuromuscular or cardiac pathology, syndromes, PCD, or CF. Figure 1 displays the distribution of the different diagnoses. There were no differences in final diagnoses between children with or without alarm symptoms.

Underlying pathology in children with recurrent respiratory in two nonacademic hospitals. ENT indicates ear-nose-throat.


Our aim was to examine the prevalence of underlying pathology in children visiting nonacademic pediatric practice because of RRTIs. Pediatricians did not detect any pathology in the vast majority of all patients (64%). In only 57% of the cases, it was recorded whether the patient was exposed to passive smoking, an important risk factor for RTI in children.4 For clinical practice, it is important to discuss risk factors such as passive smoking more extensively with all parents, so this knowledge can be used in the consideration to request or to postpone diagnostic tests or in the provision of information to parents. Pediatricians choose diagnostic testing over a ‘wait and see’ approach for the majority of patients (62%). Remarkably the choice to perform diagnostic test was not influenced by the presence or absence of alarm symptoms, which indicates that other factors, such as expectations of referring GPs to perform tests, could have played a role.

In our study, we found almost no severe underlying pathology, whereas literature reports higher prevalences of illnesses such as primary immunodeficiency (10%–16%), micro-aspiration (3%–48%), GER (5%–15%), or congenital heart disease (5%–29%).5–7 This substantial difference might be explained by the population characteristics. Previous studies mainly focused on children visiting tertiary care hospitals with lower RTIs, while, to our knowledge, our study is the first that was performed in children who visited the outpatient clinic of nonacademic hospitals because of mainly upper RRTIs. Therefore, our population might have been less likely to have an underlying condition. Most of the patients in this study had clearance or improvement of symptomatology over time. This makes it unlikely that severe diagnoses have been missed.

A limitation of this study is its retrospective design. Symptoms and risk factors might have been underreported, because some pediatricians might have discussed these topics with parents without reporting it in the electronic medical record. Also, an exact or objective measurement of the number of infectious episodes could not be made. However, this study does provide a good overall representation of the current practice of diagnostics as well as the prevalences of underlying illnesses in children who visit the outpatient clinic of a general Dutch nonacademic hospital because of upper RRTIs.


The diagnostic strategy in children with RRTIs visiting a nonacademic hospital can be a challenge for pediatricians. The prevalence of severe underlying pathology is very low and respiratory symptoms resolved spontaneously in the majority of these children. We propose that a ‘wait and see’ approach is safe in the absence of alarm symptoms. If symptoms persist or alarm symptoms occur, further diagnostic testing is warranted. There is a need for more evidence on which diagnostic tests should be done and in which order they should be performed.


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recurrent respiratory tract infections; prevalence; immunodeficiency

Supplemental Digital Content

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