Date Published: June 11, 2018
Publisher: Public Library of Science
Author(s): Yao-Te Tsai, Ethan I. Huang, Geng-He Chang, Ming-Shao Tsai, Cheng-Ming Hsu, Yao-Hsu Yang, Meng-Hung Lin, Chia-Yen Liu, Hsueh-Yu Li, Yu Ru Kou.
Studies have revealed that 3.5%–26.6% of patients with epiglottitis have comorbid diabetes mellitus (DM). However, whether preexisting DM is a risk factor for acute epiglottitis remains unclear. In this study, our aim was to explore the relationship between preexisting DM and acute epiglottitis in different age and sex groups by using population-based data in Taiwan.
We analyzed data between January 2000 and December 2013 obtained from the Taiwan National Health Insurance Research Database. The case group consisted of 2,393 patients with acute epiglottitis. The control group comprised 9,572 individuals without epiglottitis, frequency matched by sex, age, urbanization level, and income. Underlying DM was retrospectively assessed in the cases and controls. Univariate and multivariate logistic regression analyses were used to investigate the associations between underlying DM and acute epiglottitis.
Of the 2,393 patients, 180 (7.5%) had preexisting DM, whereas only 530 (5.5%) of the 9,572 controls had preexisting DM. Multivariate logistic regression analyses indicated that preexisting DM was significantly associated with acute epiglottitis (adjusted odds ratio [aOR] = 1.42, 95% confidence interval [CI] = 1.15–1.75, P = 0.004). Subgroup analysis showed that the association between DM and epiglottitis remained significant for men (aOR = 1.57, 95% CI: 1.19–2.08, p = 0.002) but not for women. Age-stratified analysis revealed a significant association between DM and acute epiglottitis in patients aged 35–64 years. Use of anti-diabetic agents was not significantly associated with the development of acute epiglottitis among diabetic patients, including oral hypoglycemic agents (OHA) alone (aOR = 0.88, 95% CI = 0.53–1.46, p = 0.616), and OHA combined with insulin/ insulin alone (aOR = 1.30, 95% CI = 0.76–2.22, p = 0.339). The association between presence of diabetes complications and the occurrence of acute epiglottitis was also not significant among diabetic patients in this study setting (aOR = 0.86, 95% CI = 0.59–1.26, p = 0.439).
The results of our large-scale population-based case–control study indicate that preexisting DM is one of the possible factors associated with the development of acute epiglottitis. Physicians should pay attention to the symptoms and signs of acute epiglottitis in DM patients, particularly in men aged 35–64 years.
Epiglottitis is the acute inflammation of the supraglottic region, including the epiglottis, arytenoids, and aryepiglottic folds. It is a true airway emergency, and without timely intervention, the supraglottic swelling may lead to life-threatening airway obstruction[1, 2] and severe complications such as sepsis, meningitis, necrotizing fasciitis, and mediastinitis.[5–8] The risk factors for epiglottitis include old age, the male sex, obesity, a preexisting epiglottic cyst, and an impaired host immune system.[9–11] Infected epiglottic cysts and impaired immunity have also been reported to increase the risk of recurrent episodes.[9, 10] The most common pathogens implicated in acute epiglottitis are bacteria such as type-b Haemophilus influenzae, alpha- and beta-hemolytic streptococci, Staphylococcus aureus, Escherichia coli, Enterobacter, Klebsiella pneumoniae, and other H. influenzae species. Other reported causes include viral infections, fungal infections, trauma by a foreign body, inhalation burns, and chemical ingestion. However, despite detailed investigation, a specific pathogen can be identified from blood or throat cultures in only 10%–25% of patients with epiglottitis.[14, 15] The incidence of pediatric epiglottitis dropped dramatically after routine use of the H. influenzae type-b (Hib) vaccine in childhood vaccination programs.[16–20] However, the incidence of acute epiglottitis in adults has been either increasing[2, 12, 16, 21] or remaining constant.[17, 22] Shah et al. conducted an 8-year retrospective review of epiglottitis admissions from 1998 to 2006 and concluded that epiglottitis continues to be a significant clinical entity in the United States and that the incidence of adult epiglottitis is increasing in two groups: those 45–64 years of age and those older than 85 years. A common perception is that in the Hib vaccine era, acute epiglottitis has become a disease of adults and that the pathogens of epiglottitis have shifted to those other than Hib.[2, 24] A considerable number of adult patients with epiglottitis have preexisting medical conditions at diagnosis, such as diabetes mellitus (DM), hypertension, and alcohol abuse, which may weaken their immunity and increase their susceptibility to infections.[12, 15, 22, 25]
Between 2000 and 2013, 2,393 newly coded patients with acute epiglottitis met the criteria for cases, and 9,572 individuals were matched as controls. Table 1 presents the intergroup demographic characteristics. No significant differences in sex, age, urbanization level, or income were observed between the groups because of frequency matching on these variables. The mean age for the total 11,965 patients was 33.6 years (standard deviation = 23.3 years). Half of the individuals were under 34 years old, and only 10.2% of the patients were over 65 years old. Among the 2,393 patients with acute epiglottitis, 180 (7.5%) had underlying DM, whereas 530 (5.5%) of the 9,572 controls had DM (p < .001). Most DM patients in both case and control groups were type 2 DM. Compared with the control group, the epiglottitis group had a higher incidence of asthma, chronic liver disease, coronary artery disease, and pneumonia and influenza, chronic obstructive pulmonary disease (COPD), autoimmune diseases, alcohol dependence and abuse, gastroesophageal reflux disease (GERD), and upper digestive tract cancer. To the best of our knowledge, this population-based case–control study is the first to elucidate the quantitative relationship between DM and acute epiglottitis. By using the nationwide population-based database, we overcame the difficulty of recruiting patients with a disease of low incidence and identified adequate numbers of epiglottitis cases with minimal selection bias, and this is because all health care services are covered by the NHI program in Taiwan. Based on the power of the large sample size, our study provides robust evidence for the higher odds ratio of underlying DM in patients with epiglottitis than in those without. To consider the effects of potential confounders, we used multivariate logistic regression after adjustment for comorbidities, including asthma, chronic liver disease, coronary artery disease, hypertension, and pneumonia/influenza, upper digestive tract cancer, autoimmune diseases, COPD, alcohol dependence and abuse, corrosive injury of upper digestive tract, and GERD, to compare the outcomes of the case and control groups. The association between DM and acute epiglottitis remained significant even after adjustment for a variety of comorbidities, and remained constant with different preexisting DM duration before the index date. Based on the results of this case control study, several comorbidities, including pneumonia and influenza, COPD, GERD, autoimmune diseases, and upper digestive tract cancer were also associated with the development of acute epiglottitis (Table 2). Therefore, it must be cautious in the interpretation of these results: although preexisting DM is a significant factor associated with the development of acute epiglottitis, other factors can play a role in contributing to the acute epiglottitis due to its multi-factorial characteristics. Subgroup analyses elucidated the significant associations between DM and acute epiglottitis in men and patients aged 35–64 years. By analyzing the use of anti-diabetic agents and aDCSI among diabetic patients in this study setting, we tried to correlate the severity of DM with occurrence of acute epiglottis. We found that among diabetic patients, taking anti-diabetic agents or not was not significantly associated with the development of acute epiglottitis. Similarly, patients with diabetes-related complications were not associated with increased occurrence of acute epiglottitis as compared to those without complication. These findings suggested the importance of blood glucose control and active management of diabetes complications regarding the occurrence of acute epiglottitis. In the future, prospective clinical trials are mandatory to elucidate the causal relationship between severity of DM and the development of acute epiglottitis. Source: http://doi.org/10.1371/journal.pone.0199036