Respiratory diseases are a group of disorders that affect the function of the respiratory system, especially the lungs. Respiratory diseases are the major leading causes of death and disability in children. Estimations show that the late diagnosis of obstructive pulmonary disease in children contributes to a majority of re-hospitalization and mortality in this age group. The five common types of respiratory diseases include acute respiratory infections, asthma, tuberculosis, lung cancer, and chronic obstructive pulmonary disease (1). Pneumonia is a common cause of death in
children and is responsible for about 1.3 milliondeaths annually. Asthma is also the most common non-acquired respiratory disease in children. Respiratory diseases in childhood can lead to chronic lung disease in adulthood; therefore, immunization in childhood can specifically reduce the prevalence and severity of lung disease in adulthood (2).
As diagnosis at the early stages of the disease can have a profound effect on the success of the treatment procedure, repeated assessment of respiratory function in children should be part of screening programs (3). The wide range of respiratory diseases and their high prevalence
can lead to severe complications and high healthcare costs. Diagnostic methods such as physical examination, lung diffusing capacity, arterial blood gases (ABGs), and spirometry have been developed for the diagnosis of respiratory illnesses (4). Most of these methods are applicable at the late stages of the disease; hence, a low-cost and highly accessible diagnostic method, that can detect respiratory illnesses at the early onset of the disease, can significantly reduce mortality and disability among patients, especially in children.
As described, there are a variety of tests available to evaluate the pulmonary function in infants and children. Some of these methods require sedation and advanced laboratory apparatuses. However, spirometry is a procedure used to diagnose, manage, and monitor various respiratory diseases and does not require sedation or advanced laboratory techniques (5, 6). Spirometry, on the other hand, is also one of the safest methods of measuring lung function and is very efficient for the evaluation of small airways (7). Because spirometry can be used to diagnose changes in the airway before any symptoms in arterial blood gas (ABG) and chest X-ray and before disease worsening, it can be considered a helpful diagnostic procedure in patients with obstructive or restrictive airway symptoms (8).
Besides all diagnostic values of spirometry, its potential in the early detection of respiratory problems in children has always been controversial. In the current study, we aimed to systematically review the role of spirometry in the early diagnosis, treatment, and follow-up of children with respiratory diseases.
2-1. Study search and inclusion criteria
In this systematic review, we aimed at the advantages and diagnostic value of spirometry in the screening of children. For this purpose, a systematic search was performed in April 2020 in electronic databases including Ovid, Science Direct, PubMed, Scopus, Web of Science, Embase, and Google Scholar. The key terms used for this purpose included “spirometry” and “diagnostic value” with all their equivalents in the keyword search. First, the search was limited to English articles, and review articles, case reports, and conference papers were excluded. Afterward, we limited the search to the pediatric age of ≤ 18 years. Finally, irrelevant articles and studies which reported adults or elder population were excluded. The search was performed by two authors independently, and any disagreement between the authors was resolved in each step by double-checking. All the procedures for study design and article selection process were performed based on the PRISMA checklist 2009, which is a reliable protocol for performing systematic reviews (9).
2-2. Data synthesis and the variables
For data synthesis, all informative data including the first author’s name, demographic information, publication date, study type, number of patients, and their mean age were extracted and are listed in Table 1 in chronological order. Furthermore, the measured variables and the main findings in each study were extracted and used for qualitative data analysis. The most important variables include forced expiratory volume in 1 second (FEV1), total lung capacity (TLC), forced vital capacity (FVC), and forced expiratory flow at 25-75% of the pulmonary volume (FEF25–75%).
A total of 811 articles were found through a database search, of which 770 and 29 articles were found respectively in PubMed and Scopus, as the two major databases. Additional 12 articles were found in other databases. Also, three articles were found through manual screening of the reference list of the previously included articles. After the exclusion of irrelevant papers in several steps, a total of 19 related articles were collected for qualitative analysis, of which 4 articles were retrospective, 7 were prospective cohort, 7 were cross-sectional, and 1 article was a randomized controlled trial. The step-by-step article selection procedure is presented in Figure 1.
Overall, 3813 patients had been enrolled in the included studies, of whom 989 were male, 807 were female, and the sex of 2017 patients had not been mentioned. The age of patients varied between 6 months and 18 years. Only in one study, the age range was ≤ 20 years. Demographic information and general data of the included articles are presented in Table 1.
Based on the findings of the included studies, the results can be categorized into four groups:
1.Studies that were entirely in favor of spirometry;
2.Documents that denied the predictive role of spirometry for future respiratory illnesses;
3.Studies that did not have a conclusive finding and recommended further evaluation;
4.Studies that did not find a diagnostic value but still recommended spirometry due to providing valuable complementary results.
Considering the categories above, 12 articles were in favor of spirometry which reported a predictive value for spirometry in the early detection of respiratory illnesses. These studies Besides, 2 articles with a total of 1192 patients reported that spirometry alone does not predict future pulmonary conditions, but it was recommended since it can provide very useful complementary information that can be used for such a purpose. The results of these studies suggested that abnormal spirometric values between the age of 8 and 12 years cannot be considered as a predictor of mortality and morbidity caused by a respiratory illness in near future (13). The most prevalent diseases among the pediatric population include
The present study showed that the prevalence of febrile seizures was associated with gender, living place, temperature, family history of seizure, and the serum level of zinc. In this regard, the frequency of zinc deficiency was higher in patients with febrile seizures compared to febrile patients without seizure, before and after adjusting for gender.
Zinc plays a vital role in the neuronal terminals of the hippocampus and amygdala by producing pyridoxal phosphate and affecting glutamatergic, gamma-aminobutyric acidergic (GABAergic), and glycinergic synapses (13).
Glutamic acid decarboxylase (GAD) acts as a major inhibitory neurotransmitter in the synthesis of gamma-aminobutyric acid (GABA) (14). A study by Ganesh R. and Janakiraman L. on 38 children with febrile convulsion and 38 children as a control group, aged between 3 months and 5 years, indicated that a serum zinc deficiency was significantly more prevalent in their case group than in the control group (15). Another study has reported that there is a correlation between disruption in Zn2+ homeostasis and fever seizure (16).
In studies by Papierkowski A., Mollah M.A., and Gündüz Z. et al., the mean serum zinc level in the febrile convulsion group was significantly lower than in the control group, which indicates the role of zinc in febrile seizure. Comparing the groups in terms of age and gender, no significant difference was found, similar to our study (17-19). Abdel Hameed Z.A. et al. (20), in a study on 100 infants in Egypt, observed that temperature had no significant difference between the case and control groups. But Berg A.T. (21), Ahmed B.W. (22), and our study showed the importance of temperature in febrile seizure. The geographic area can be the cause of this difference. Duangpetsang J. in a study from 2014 to 2017 reported that a high fever with electrolyte disturbance hyponatremia has an important role in FS (23). Sharifi R. et al., in a study in 2007-2014, showed the importance of family history in febrile seizure (24), which is similar to our results.
The findings of this study show that zinc deficiency is significantly associated with the occurrence of febrile seizures. Zinc supplementation in children can therefore be helpful for the prevention and treatment of FS.
Conflict of interest
The authors declare no conflicts of interest.