key: cord-0054490-h4tv7p40
authors: Üzüm, Özlem; Kanık, Ali; Eliaçık, Kayı; Hortu, Hacer Örsdemir; Demirçelik, Yavuz; Yan, Mehmet; Helvacı, Mehmet; Demir, Belde Kasap
title: Comparison of clinically related factors and treatment approaches in patients with acute bronchiolitis
date: 2020-12-16
journal: Turk Pediatri Ars
DOI: 10.14744/turkpediatriars.2020.46144
sha: 698b04979f5562c1f45a6dc2ab564d1df7a0bc3a
doc_id: 54490
cord_uid: h4tv7p40

AIM: Acute bronchiolitis is a lower respiratory tract infection caused by viral agents in children aged under two years. Treatment includes hydration, oxygen, nebulized salbutamol, and intravenous steroids. This study aimed to determine the clinically related factors, the effect of viral agents on the clinical picture, and the efficacy of treatment methods in patients admitted with acute bronchiolitis. MATERIAL AND METHODS: Patients aged under two years of age who were hospitalized with a diagnosis of moderate/severe acute bronchiolitis between March 2015 and March 2019 were included in the study. Demographic data, hospitalization time, body temperature, presence of congenital heart disease, history of atopy, acute-phase reactants, mean platelet volume values, and respiratory virus panel results were recorded. The treatment modalities, length of hospitalization, intensive care hospitalization, and high-flow nasal cannula oxygen therapy (HFNC) were recorded. RESULTS: Four hundred twenty-two patients were included in the study. The duration of hospitalization was found to be significantly longer in patients aged under one year and in patients with acyanotic congenital heart disease. A single viral agent was detected in 69 (51.9%) patients. Rhinovirus was detected in 70 patients and RSV was detected in 37. The duration of hospitalization was found to be significantly shorter in patients who received only oxygen and/or intravenous fluid treatment compared with those who received nebulized salbutamol and/or intravenous steroids. In addition, and there was no significant difference between the groups in terms of HFNC and hospitalization in the intensive care unit. CONCLUSION: Rhinovirus was the most common cause of acute bronchiolitis in our study. It was observed that congenital heart disease prolonged the length of hospitalization. In the treatment approaches, it was observed that hydration and oxygen therapy were sufficient treatment methods for the patients, in accordance with the recommendations of the American Academy of Pediatrics, and giving nebulized therapy prolonged the hospitalization period due to the treatment discontinuation steps.

Acute bronchiolitis is a lower respiratory tract infection characterized by inflammation and edema in the small airways that occur frequently in children younger than 2 years (1) (2) (3) . Viral agents are most commonly involved in the etiology, and respiratory syncytial virus (RSV) is responsible for 50% of the cases (1, 4, 5) . The clinical picture may be more severe in patients with immune deficiency, chronic lung disease, congenital heart disease, and a history of preterm birth. It was found that laboratory tests [increased white blood cell count, C-reactive protein (CRP) values, mean platelet volume (MPV)] and respiratory virus typing did not affect predicting the severity of clinical picture (1, 6, 7) .

There are different approaches in the treatment of bronchiolitis. In the latest guidelines published by the American Academy of Pediatrics (AAP), the mainstay of treatment includes oral/intravenous hydration and oxygen support (1) . Although it has been reported that nebulized salbutamol, nebulized adrenaline, nebulized steroid or intravenous steroid treatment do not affect the duration or severity of the clinical picture, these therapies are used in many centers and continued, if a response is obtained (1, (8) (9) (10) .

In this study, we aimed to examine the demographic characteristics, symptoms, acute-phase reactants, and treatments in patients hospitalized because of acute bronchiolitis, to determine clinically related factors and the effect of viral agents on the clinical picture, and to retrospectively compare the efficiencies of different treatment modalities.

Patients aged under two years who presented with symptoms of cough, tachypnea, wheezing and dyspnea, who were hospitalized with a diagnosis of moderate/severe acute bronchiolitis between March 2015 and March 2019 were included in our study. The clinical data were retro-spectively obtained from patient registries. The demographic data, hospitalization seasons and years, presence of fever and cough, presence of acyanotic heart disease and atopy, family history of atopy, and the presence of a sibling who was followed up with a diagnosis of wheezy infant, were recorded. White blood cell count, neutrophil count, lymphocyte count, CRP, MPV values, and viruses detected in a respiratory virus panel among laboratory tests, treatment methods performed, hospitalization durations, if high-flow nasal cannula oxygen therapy (HFNC) was performed, and intensive care hospitalizations were recorded. Patients who had cyanotic congenital heart disease, received treatment with a diagnosis of recurrent acute bronchiolitis (patients who had been followed up with a diagnosis of acute bronchiolitis for ≥3 times), were being followed up because of wheezing for longer than one month, and had chronic lung disease, were not included in the study.

Patients with a diagnosis of moderate and severe acute bronchiolitis who have tachypnea and need intravenous/ oral hydration are followed up in our clinic. These patients are discharged when full oral feeding is achieved and when there is no need for oxygen. Before the guidelines and recommendations have been published by the American Academy of Pediatrics (AAP) in 2014, treatment was based on the Turkish Thorax Association's 'Consensus Report on the Diagnosis and Treatment of Acute Bronchiolitis,' and nebulized salbutamol and intravenous steroid treatments were used intensively (1, 10) . After 2014, treatment amendments came to the forefront following the AAP recommendations (1). Between March 2015 and March 2019, the period in which the study was conducted, treatments were adjusted according to clinicians' preference of guideline, independent of the severity of the clinical picture. In our study, the patients were divided into two groups as patients who received nebulized salbutamol and/or intravenous steroid in addition to oxygen and/or intravenous fluid treatment (group 1) and those who received oxygen and/or intravenous fluid treatment alone patients aged under one year and in patients with acyanotic congenital heart disease. A single viral agent was detected in 69 (51.9%) patients. Rhinovirus was detected in 70 patients and RSV was detected in 37. The duration of hospitalization was found to be significantly shorter in patients who received only oxygen and/or intravenous fluid treatment compared with those who received nebulized salbutamol and/or intravenous steroids. In addition, and there was no significant difference between the groups in terms of HFNC and hospitalization in the intensive care unit.

Rhinovirus was the most common cause of acute bronchiolitis in our study. It was observed that congenital heart disease prolonged the length of hospitalization. In the treatment approaches, it was observed that hydration and oxygen therapy were sufficient treatment methods for the patients, in accordance with the recommendations of the American Academy of Pediatrics, and giving nebulized therapy prolonged the hospitalization period due to the treatment discontinuation steps.

Keywords: Bronchiolitis, rhinovirus, salbutamol, steroid doğuştan kalp hastalığı olan olguların yatış süreleri anlamlı olarak uzun saptandı. Olguların 69'unda (%51, 9) tek viral etken saptandı. Olguların 70'inde Rinovirüs, 37'sinde respiratuar sinsityal virüs saptandı. Sadece oksijen ya/ya da damariçi sıvı tedavisi alanların yatış süreleri, bu tedavilerin yanında nebulize salbutamol ya/ya da damariçi steroid alanlarda anlamlı düzeyde kısa olduğu, YANKOT ve yoğun bakım yatış için iki grup arasında anlamlı fark olmadığı görüldü. Çıkarımlar: Çalışmamızda akut bronşiolit etkenleri arasında en sık Rinovirüs saptandı. Doğuştan kalp hastalığının yatış süresini uzattığı görüldü. Tedavi yaklaşımlarında ise Amerikan Pediatri Akademisi önerileri ile uyumlu olarak, hidrasyon ve oksijen tedavisinin olgular için yeterli tedavi yöntemi olduğu ve nebulize tedavi vermenin tedavi kesme basamakları nedeni ile yatışı süresini uzattığı görüldü.

Anahtar sözcükler: Bronşiolit, rinovirüs, salbutamol, steroid (group 2). The effect of the AAP guideline on hospitalization duration, need for HFNC, and need for hospitalization in the intensive care unit (ICU), was evaluated. HFNC treatment is initiated in patients hospitalized in our ward with a diagnosis of moderate/severe bronchiolitis whose respiratory distress persists, oxygen saturation is below 93% or who have respiratory acidosis despite treatment methods preferred by physicians. The study was conducted in accordance with the principles of the Helsinki Declaration and approval was obtained from the local ethics committee (10.04.2019, decision No: 2019/6-13). The data were obtained from patient records. Therefore, informed consent was not obtained.

Analyses of the present data were performed using the IBM Statistical Package for the Social Sciences Ver. 24 program (SPSS, Chicago, IL, USA) according to group characteristics. Before analysis of the data related to the variables included in case form, their compatibility with normal distribution was examined considering the number of cases using primarily the Shapiro-Wilk and Kolmogorov-Smirnov tests, and subsequently using Skewness and Kurtosis values. After the assumption was provided that the data were distributed normally, the Fisher's exact, Chi-square and Student t-tests were used in the comparison of the mean values of two independent groups. The Mann-Witney U test was used for variables that did not have normal distribution. In all statistical tests, a p-value of 0.05 was considered statistically significant.

Four hundred twenty-two patients were included in the study. It was observed that 60.7% of the subjects were male and the mean age was 8.04 (±5.33) months (Table  1 ). There was no significant difference between the male and female subjects in terms of hospitalization duration, HFCN treatment, and hospitalization in the ICU. When the subjects were evaluated in two groups as those aged under and over one year of age, the hospitalization duration was found to be significantly longer in the group aged under one year (Table 2 ). It was found that 213 (50.6%) of the subjects presented in winter months and 95 (22.3%) presented in autumn months. It was observed that 74.2% of the subjects had a birth weight of 2500 g and over and 18.2% had a family history of atopy. The subjects' clinical and demographic data are summarized in Table 1 . The subjects who had a history of preterm birth, low birth weight (LBW), acyanotic heart disease, atopy, a family history of atopy, and had a sibling who had been followed up with a diagnosis of wheezy infant, were compared in terms of hospitalization duration, need for HFCN and hospitalization in the ICU. Among the clinically related factors, only subjects who had congenital heart disease were observed to have longer hospitalization duration and more prolonged need for HFCN (Table 2 ).

It was observed that 188 (44.5%) of the subjects had a body temperature above 38°C at the time of the first presentation and 389 (92.1%) had cough. No significant difference was observed between the subjects who did and did not have fever in terms of hospitalization duration, need for HFCN and hospitalization in the ICU. In the classification made according to oxygen saturation, it was observed that the need for HFCN was significantly higher in the subjects who had an oxygen saturation below 93% (Table 2) . The subjects' white cell counts, CRP, and MPV values were compared. No significant difference was found between the subjects who had high acute-phase reactants and high MPV values and the those who had normal values in terms of the need for HFCN and hospitaliza-tion in the ICU. When the subjects' neutrophil/lymphocyte ratios (NLR) and white blood cell/MPV ratios were compared, no significant difference was found between subjects who did and did not need hospitalization in the ICU or HFCN. 

It was observed that respiratory virus panel was obtained from 133 (32%) of the subjects and no viral agent was found in 15 subjects. A single viral agent was found in 69 subjects (59%), and multiple viral agents were detected in 49 (368%) subjects. The most common viral agent was found to be rhinovirus (77 subjects, 44%). Respiratory syncytial virus was found in 38 subjects (22.6%) ( Table 3) . Among the subjects in whom a viral agent was found in the respiratory virus panel, six were hospitalized in the ICU; rhinovirus was found in four of these subjects and RSV A and rhinovirus were found in two subjects (Table  3) . HFCN, hospitalization in the ICU, and hospitalization durations related to the viral agents detected are shown in Table 3 . Hospitalization duration and HFCN were evaluated between single viral agents and multiple viral agents, and no significant difference was found between the two groups ( Table 4 ). The subjects were divided into two groups as patients in whom RSV and non-RSV viral agents were found and those in whom rhinovirus and non-rhinovirus viral agents were found, and need for HFCN was observed to be significantly higher in subjects in whom RSV was found (Table 4 ). These subjects were not compared in terms of hospitalization in the ICU because these subjects were those in whom rhinovirus and RSV were found.

When the treatment performed to the subjects was evaluated, it was observed that all subjects received intravenous fluid therapy at the time of hospitalization, 252 subjects received oxygen treatment, 212 subjects received nebulized salbutamol treatment, and 87 subjects received both nebulized salbutamol and intravenous steroid treatment. The subjects were divided into two groups as the those who received nebulized salbutamol and intravenous steroid treatment in addition to oxygen and/or intravenous fluid therapy (group 1) and patients who received oxygen and/or intravenous fluid therapy alone (group 2). When evaluated by years, it was observed that the AAP treatment approaches in our clinic (oxygen and/or intravenous fluid treatment) increased from 12.3% to 62.3% in four years. Gestational week, birth weight, association with acyanotic congenital heart disease, history of atopy, family history of atopy, and history of a sibling who had been followed up with a diagnosis of wheezy infant, were compared to evaluate the groups' distribution and no significant difference was found between the groups. HFCN therapy, hospitalization in the ICU, and hospitalization durations were evaluated between the groups. It was observed that the hospitalization duration was significantly shorter in group 2 and no significant difference was found between the two groups in terms of HFCN and hospitalization in the ICU (Table 4 ).

In our study, the subjects were compared in terms of hospitalization duration, need for HFCN, and need for hospitalization in the ICU by risk groups. It was observed that being aged under one year or the presence of congenital heart disease significantly prolonged hospitalization duration, and the presence of congenital heart disease, RSV positivity, and oxygen saturation below 93% at the time of presentation significantly increased the need for HFCN. Also, it was found that there was no difference between the subjects who did and did not receive nebulized salbutamol and/or intravenous steroid treatment in terms of the need for HFCN or the need for hospitalization in the ICU, and hospitalization duration prolonged significantly in subjects who received these additional therapies.

In our study, the number of male patients was significantly higher and no difference was found between the sexes in terms of hospitalization duration, need for HFCN, and need for hospitalization in the ICU. Acute bronchiolitis affects children aged younger than two years and most frequently peaks between 2 and 12 months (11) . The AAP reported that acute bronchiolitis occurred more frequently in children aged younger than 12 months in its reviews and guidelines, and recommended close monitoring in this group because it carried risk (1). In our study, the hospitalization duration was found to be longer in children aged younger than 1 year. Studies in the literature have reported that acute bronchiolitis occurred more frequently in boys, but no difference has been reported between the sexes in terms of clinical severity. Some studies reported that the higher frequency in boys might be explained by the fact that the ratio of airway lumen diameter to lung volume is smaller in boys compared with girls (12, 13) .

When LBW babies were compared with babies with normal birth weight in our study, but no significant difference was found in terms of hospitalization duration, need for hospitalization in the ICU, and need for HFCN. In the literature, children with a history of preterm birth, car- (1, 11, 14) . Apnea may develop and high mortality/morbidity rates may be observed, especially in babies with a history of preterm birth (15) . Low birth weight is among the risk factors for acute bronchiolitis, and many studies have reported that hospitalization duration is prolonged and disease severity is higher in this group (16, 17) . In a study conducted by Turan et al. (13) , however, no significant difference was found between LBW babies and babies with normal birth weight in terms of the number of acute bronchiolitis episodes.

In our study, it was observed that two-thirds of the subjects presented in winter months. Respiratory viruses are observed more frequently throughout winter months and infection becomes easier due to the increase in the time spent by children in closed areas (14) . Following winter months, acute bronchiolitis peaks at the beginning of spring. This increase in the number of cases is in parallel to the RSV season (18) .

In our study, no significant difference was found between the subjects who did and did not have a family history of atopy in terms of clinical course and hospitalization duration. There are studies in the literature showing that the clinical course of bronchiolitis was more severe in subjects who had a history of atopy, and subjects with a family history of eczema among atopy findings had a more severe clinical picture compared with controls, but the clinical picture was not different among subjects with a family history of asthma and allergic rhinitis (14, 19) . In a study conducted with subjects who did and did not have bronchiolitis, no significant difference was found between the two groups in terms of family history of allergic rhinitis, eczema, and asthma (14) .

In our study, multiple vital agents were found in one-third of the subjects in whom a respiratory panel was obtained.

In addition, RSV was observed in one-third of the subjects and rhinovirus was found to be the most common agent. In clinical assessments, it was found that the need for HFCN was higher in RSV-positive subjects. RSV positivity ranges between 30% and 80% in patients diagnosed as having acute bronchiolitis, and RSV ranks first in many studies (11, 20, 21) . In a study conducted in our country, it was observed that one-third of the subjects were RSV positive (22) . In a study conducted by Ramagopal et al. (23) , the subjects who were diagnosed as having bronchiolitis were divided into two groups as RSV and non-RSV, and no difference was found in terms of prematurity, physical examination findings, acute-phase reactants, and supportive oxygen treatment, whereas the hospitalization duration was found to be significantly longer in RSV-positive subjects. In addition, recent studies showed that the number of subjects in whom rhinovirus was found was close to the number of subjects in whom RSV was found among children who presented with bronchiolitis and wheezing (24) (25) (26) . In a study conducted by Janahi et al. (7), multiple viral agents were found in 33% of the subjects. In a study conducted by Kanık et al. (27) , a single viral agent was found in 55.3% of the subjects, and no difference was found in hospitalization duration between the subjects with single and multiple viral agents. In our study, viral agents were evaluated in single and multiple groups, and similar agents were observed between the two groups.

In our study, it was observed that white blood cell count, CRP, MPV, neutrophil/lymphocyte ratio (NLR), and WBC/ MPV values were not efficient in predicting the need for hospitalization in the ICU and need for HFCN in patients with a diagnosis of acute bronchiolitis. It has been stated that WBC and CRP values are not significant for making a diagnosis of acute bronchiolitis, and additional investigations are not necessary in outpatients (1) . However, some studies showed that the CRP values were higher in patients with acute bronchiolitis compared with healthy individuals (28) . Although the hospitalization duration was found to be longer in patients with increased CRP and WBC values, there are some studies showing that the WBC count was within the normal range by age in patients with acute bronchiolitis (1, 11, 29) . In studies that investigated the relationship between bronchiolitis and MPV, the MPV value was found to be higher in healthy children and no difference was found between subjects who had mild, moderate, and severe bronchiolitis. It was thought that it would be more appropriate to make comparisons using follow-up MPV values in addition to instantaneous measurements of MPV values (6, 30) .

In recent years, the effects of the ratios of some values in the complete blood count to each other on specifying clinical severity and predicting hospitalization process, have been investigated. As the values in the complete blood count are more easily accessible compared with other values, they are investigated in terms of efficiency of use (31) . For example, NLR and the WBC/MPV ratio were found to be higher in subjects who had a diagnosis of bronchiolitis compared with healthy individuals, and neutrophil and NLR values were found to be significantly higher in subjects with severe bronchiolitis compared with subjects with mild bronchiolitis in a study involving 34 healthy children and 77 subjects with bronchiolitis. With this result, it was advocated that NLR values might have prognostic importance (28) . No studies have reported the limits for these ratios; it has only been shown that they may be higher compared with healthy individuals or with clinical severity. The fact that the number of subjects in our study was higher compared with the present literature suggested that the relationship between NLR and acute bronchiolitis should be reevaluated with large sample sizes.

In our study, no difference was found between the subjects who received treatment methods other than hydration and oxygen therapies in terms of the need for HFCN and need for hospitalization in the ICU. The hospitalization duration was found to be significantly longer in the group that received nebulized salbutamol and intravenous steroid treatment. The AAP stated that hydration and oxygen treatment was efficient treatment for acute bronchiolitis, and many meta-analyses have shown that nebulized salbutamol and intravenous corticosteroids were not efficient in acute bronchiolitis (1, 32, 33) . In addition, it has been reported that the adverse effects (tachycardia, arrhythmia) of these medical therapies used complicate clinical monitoring (1). However, some authors recommend that systemic steroid should be tried in treatment management if the picture of acute bronchiolitis cannot be differentiated from an acute asthma attack (34) . In particlular, hydration has been reported to be the first-line treatment to compensate dehydratation occurring as a result of fever and underfeeding in children with acute bronchiolitis (35) . In a study conducted by Mussman et al. (36) , bronchodilator treatment and respiratory scores were compared, and no significant difference was found between the groups. Considering that clinically related factors were found to be similar between the two groups and thre treatment choices of physicians were not made according to clinical severity (some patients did not receive nebulized salbutamol, though they continuously needed oxygen, and patients who received nebulized salbutamol despite never needing oxygen), the fact that need for HFCN and hospitalization in the ICU was similar in the two groups in our study supported the assumption that the approach of oxygen plus hydration therapy was sufficient in these patients as indicated in the AAP guidelines. In addition, it was thought that the process of treatment decrement prolonged hospitalization duration in the subjects in whom nebulized salbutamol and intravenous steroid treatment were initiated.

As our study was conducted by patient records, risk factors for acute bronchiolitis such as breastfeeding duration, socioeconomical level and exposure to cigarette smoking in the family, could not be evaluated due to insufficient specification. In addition, acute bronchiolitis clinical severity scores at the time of admission and at the time of discharge could not be obtained from the patient records. Although it was found that the parameters and ratios evaluated in complete blood counts and acute-phase reactants were not efficient in predicting the need for HFCN and hospitalization in the ICU, these values were not compared with those of healthy children as done in other studies.

In conclusion, clinically related factors were evaluated in patients with acute bronchiolitis in our study and it was observed that LBW, preterm birth, a personal or family history of atopy, presence of fever, and increased acute-phase reactants were not correlated with hospitalization duration, HFCN, and hospitalization in the ICU. In addition, it was found that the hospitalization duration was longer in subjects younger than one year or in subjects with congenital heart disease, and the need for HFCN was higher in the subjects with RSV positivity, congenital heart disease or an oxygen saturation below 93% at the time of presentation. Also, it was observed that there was no difference between subjects who did and did not receive nebulized salbutamol and/or intravenous steroid in terms of the need for HFCN and hospitalization in the ICU, and the hospitalization duration was significantly longer in subjects who received these additional therapies. In light of this information, it was thought that the AAP recommendations were sufficient in general treatment approaches, and increased rate of application of these recommendations in our clinic was appropriate. Informed Consent: The data were obtained from patient records, therefore informed consent was not obtained.

Externally peer-reviewed. 

The authors have no conflicts of interest to declare. 

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