The hygiene hypothesis, first proposed in 1989, suggested that reduced exposure to infections in early life leads to allergic diseases by the defects in the establishment of immune tolerance. Although many studies provided evidence that some exposure conditions, including family size, antibiotics, probiotics, and viral or bacterial infections, are strongly related to the prevalence of allergic diseases, thereby supporting the hygiene hypothesis, some evidence does not provide acceptable results for the hygiene hypothesis. Further, most studies have focused on patients with asthma or atopic dermatitis, not allergic rhinitis. In this review, we summarize the recent studies for and against the ‘hygiene hypothesis’ and identify causal association with the prevalence of allergic rhinitis.

Allergic rhinitis (AR) is a type of rhinitis accompanied by sensitization to allergens. One of the most clinically important allergens is pollen. Recently, due to climate change and CO 2 air pollution, the flowering period starts earlier and persists longer. In addition, antigenicity due to environmental pollution is also being strengthened. As a result, the sensitization rate to pollen antigens is on the rise. It is known that the prevalence of AR especially caused by pollen is rapidly escalating. Although the causal relationship between pollen exposure and the severity of rhinitis is not precisely established, an association of rhinitis symptoms with the time of pollen scattering exists. In addition, the mixed effect of environmental pollution and pollen may play a role in the development of rhinitis symptoms. Therefore, in order to avoid pollen, it is necessary to constantly improve pollen forecast and minimize the contact with pollen indoors and outdoors. Treatment of AR should be performed according to guidelines. Also, continuous efforts to solve the environmental problems affecting the ecology of pollen are needed.

Background: Recent reports have suggested that pneumonitis is a rare complication following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).However, its clinical features and outcomes are not well known. The aim of this study was to identify the clinical characteristics and outcomes of patients with vaccine-associated pneumonitis following vaccination against SARS-CoV-2. Methods: In this nationwide multicenter survey study, questionnaires were distributed to pulmonary physicians in referral hospitals. They were asked to report cases of development or exacerbation of interstitial lung disease (ILD) associated with the coronavirus disease 2019 vaccine. Vaccine-associated pneumonitis was defined as new pulmonary infiltrates documented on chest computed tomography within 4 weeks of vaccination and exclusion of other possible etiologies. Results: From the survey, 49 cases of vaccine-associated pneumonitis were identified between February 27 and October 30, 2021. After multidisciplinary discussion, 46 cases were analyzed. The median age was 66 years and 28 (61%) were male. The median interval between vaccination and respiratory symptoms was 5 days. There were 20 (43%), 17 (37%), and nine (19%) patients with newly identified pneumonitis, exacerbation of pre-diagnosed ILD, and undetermined pre-existing ILD, respectively. The administered vaccines were BNT162b2 and ChAdOx1 nCov-19/AZD1222 each in 21 patients followed by mRNA-1273 in three, and Ad26.COV2.S in one patient. Except for five patients with mild disease, 41 (89%) patients were treated with corticosteroid. Significant improvement was observed in 26 (57%) patients including four patients who did not receive treatment. However, ILD aggravated in 9 (20%) patients despite treatment. Mortality was observed in eight (17%) patients. Conclusion These results suggest pneumonitis as a potentially significant safety concern for vaccines against SARS-CoV-2. Clinical awareness and patient education are necessary for early recognition and prompt management. Additional research is warranted to identify the epidemiology and characterize the pathophysiology of vaccine-associated pneumonitis.

Background: Alpha-toxin (AT), a major virulence factor of Staphylococcus aureus, is an important immunotherapeutic target to prevent or treat invasive S. aureus infections. Previous studies have suggested that anti-AT antibodies (Abs) may have a protective role against S. aureus bacteremia (SAB), but their function remains unclear. Therefore, we aimed to investigate the association between serum anti-AT Ab levels and clinical outcomes of SAB. Methods: Patients from a prospective SAB cohort at a tertiary-care medical center (n = 51) were enrolled in the study from July 2016 to January 2019. Patients without symptoms or signs of infection were enrolled as controls (n = 100). Blood samples were collected before the onset of SAB and at 2- and 4-weeks post-bacteremia. Anti-AT immunoglobin G (IgG) levels were measured using an enzyme-linked immunosorbent assay. All clinical S. aureus isolates were tested for the presence of hla using polymerase chain reaction. Results: Anti-AT IgG levels in patients with SAB before the onset of bacteremia did not differ significantly from those in non-infectious controls. Pre-bacteremic anti-AT IgG levels tended to be lower in patients with worse clinical outcomes (7-day mortality, persistent bacteremia, metastatic infection, septic shock), although the differences were not statistically significant. Patients who needed intensive care unit care had significantly lower anti-AT IgG levels at 2 weeks post-bacteremia (P = 0.020). Conclusion The study findings suggest that lower anti-AT Ab responses before and during SAB, reflective of immune dysfunction, are associated with more severe clinical presentations of infection.

Background: Exposure to cadmium and mercury is associated with renal dysfunction. This study aimed to investigate the possible ability of dietary education to decrease blood cadmium and mercury levels in patients with chronic kidney disease (CKD). Methods: Twenty-seven patients with CKD were enrolled in this prospective, single-arm pilot study. Patients with blood cadmium levels ≥1.4 μg/L were instructed to reduce their intake of shellfish, while those with blood mercury levels ≥5.0 μg/L were asked to reduce their intake of externally blue-colored fish. Results: Seven dialysis patients and 15 pre-dialysis patients completed the study. Compared with baseline, the blood cadmium (2.0±0.7 μg/L vs. 1.8±0.7 μg/L, p=0.031) and mercury levels (4.4±2.6 μg/L vs. 3.5±1.9 μg/L, p=0.005) after 1 year significantly decreased, although the dietary intake was not significantly different in patients with blood cadmium levels ≥1.4 μg/L and blood mercury levels ≥5.0 μg/L. In pre-dialysis patients, kidney function worsened after 1 year compared with that at baseline despite the reduction in blood cadmium and mercury levels. Conclusions Reduction of food intake containing cadmium and mercury may lower the blood cadmium and mercury levels in CKD patients with higher cadmium and mercury levels. Higher blood cadmium levels may cause renal disease progression in pre-dialysis patients, and further studies are necessary to determine the underlying mechanisms.

Background: This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin. Methods: In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks. Results: The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted. Conclusion Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

Background: Although coronavirus disease 2019 (COVID-19) is a viral infection, antibiotics are often prescribed due to concerns about accompanying bacterial infection. Therefore, we aimed to analyze the number of patients with COVID-19 who received antibiotic prescriptions, as well as factors that influenced antibiotics prescription, using the National Health Insurance System database. Methods: We retrospectively reviewed claims data for adults aged ≥ 19 years hospitalized for COVID-19 from December 1, 2019 to December 31, 2020. According to the National Institutes of Health guidelines for severity classification, we calculated the proportion of patients who received antibiotics and the number of days of therapy per 1,000 patient-days. Factors contributing to antibiotic use were determined using linear regression analysis. In addition, antibiotic prescription data for patients with influenza hospitalized from 2018 to 2021 were compared with those for patients with COVID-19, using an integrated database from Korea Disease Control and Prevention Agency-COVID19-National Health Insurance Service cohort (K-COV-N cohort), which was partially adjusted and obtained from October 2020 to December 2021. Results: Of the 55,228 patients, 46.6% were males, 55.9% were aged ≥ 50 years, and most patients (88.7%) had no underlying diseases. The majority (84.3%; n = 46,576) were classified as having mild-to-moderate illness, with 11.2% (n = 6,168) and 4.5% (n = 2,484) having severe and critical illness, respectively. Antibiotics were prescribed to 27.3% (n = 15,081) of the total study population, and to 73.8%, 87.6%, and 17.9% of patients with severe, critical, and mild-to-moderate illness, respectively. Fluoroquinolones were the most commonly prescribed antibiotics (15.1%; n = 8,348), followed by third-generation cephalosporins (10.4%; n = 5,729) and beta-lactam/beta-lactamase inhibitors (6.9%; n = 3,822). Older age, COVID-19 severity, and underlying medical conditions contributed significantly to antibiotic prescription requirement. The antibiotic use rate was higher in the influenza group (57.1%) than in the total COVID-19 patient group (21.2%), and higher in severe-to-critical COVID-19 cases (66.6%) than in influenza cases. Conclusion Although most patients with COVID-19 had mild to moderate illness, more than a quarter were prescribed antibiotics. Judicious use of antibiotics is necessary for patients with COVID-19, considering the severity of disease and risk of bacterial co-infection.