Two Years of Experience and Methodology of Korean COVID-19 Living Clinical Practice Guideline Development.

BACKGROUND: In Korea, during the early phase of the coronavirus disease 2019 (COVID-19) pandemic, we responded to the uncertainty of treatments under various conditions, consistently playing catch up with the speed of evidence updates. Therefore, there was high demand for national-level evidence-based clinical practice guidelines for clinicians in a timely manner. We developed evidence-based and updated living recommendations for clinicians through a transparent development process and multidisciplinary expert collaboration. METHODS: The National Evidence-based Healthcare Collaborating Agency (NECA) and the Korean Academy of Medical Sciences (KAMS) collaborated to develop trustworthy Korean living guidelines. The NECA-supported methodological sections and 8 professional medical societies of the KAMS worked with clinical experts, and 31 clinicians were involved annually. We developed a total of 35 clinical questions, including medications, respiratory/critical care, pediatric care, emergency care, diagnostic tests, and radiological examinations. RESULTS: An evidence-based search for treatments began in March 2021 and monthly updates were performed. It was expanded to other areas, and the search interval was organized by a steering committee owing to priority changes. Evidence synthesis and recommendation review was performed by researchers, and living recommendations were updated within 3-4 months. CONCLUSION: We provided timely recommendations on living schemes and disseminated them to the public, policymakers and various stakeholders using webpages and social media. Although the output was successful, there were some limitations. The rigor of development issues, urgent timelines for public dissemination, education for new developers, and spread of several new COVID-19 variants have worked as barriers. Therefore, we must prepare systematic processes and funding for future pandemics.

Dose-Response Relationship between Environmental Exposure to Nickel and Pulmonary Function in the Korean General Population Aged 40 or Older.

Nickel is a well-known skin allergen; however, few studies to date have investigated the association between nickel exposure and lung function impairment. The present study, therefore, evaluated the relationship between blood nickel concentrations and lung function profiles in the Korean general population (n = 1,098). Dose-response relationships between blood nickel quartiles and pulmonary function were assessed by sex in multivariate models, after adjustment for potentially confounding factors such as age, height, and smoking status. Quartiles of blood nickel concentrations were significantly associated with markers of pulmonary function in Korean men, such as forced expiratory volume in 1 second (FEV1) and forced expiratory flow 25-75% (FEF25-75%). Relative to the first quartile, the estimated coefficients (standard error (SE)) of blood nickel levels for FEV1 in the third and fourth quartiles of Korean men were -126.6 mL (59.1) and -138.5 mL (59.8), respectively (p < 0.05). Relative to the first quartile, the estimated coefficients (SE) of blood nickel levels for FEF25-75% in the second and fourth quartiles were -244.9 mL (109.5) and -266.8 mL (111.5), respectively (p < 0.05). Dose-response relationships were observed between quartiles of blood nickel concentrations and the pulmonary function markers FEV1 and FEF25-75% in Korean men aged 40 or older.

Comparison of Long Term Follow-up Chest CT Imaging in Adult and Pediatric Patients with Humidifier Disinfectant-related Lung Injury.

BACKGROUND: To compare the chest computed tomography (CT) images of children and adults in families with clusters of humidifier disinfectant-related lung injury (HDLI) after cessation of exposure to humidifier disinfectant (HD). METHODS: We reviewed medical records of 19 families with 43 patients (21 adults, 22 children) among families, which had at least one adult and one child with HDLI. Each family was exposed to the same HD exposure environment. RESULTS: In adults, centrilobular nodules were predominant (95.2%) in chronic HDLI findings after cessation of exposure to HD, however, in children, normal pattern was most prevalent on chest CT (45.5%), followed by centrilobular nodule (36.4%), bizarre lung cysts (36.4%), and reticulation (13.6%). CONCLUSION: Unlike the known chronic HDLI finding of adults, centrilobular nodules were only present in 36.4% of children. The frequency of bizarre lung cysts were significantly greater in children than that in adults after cessation of similar exposure to HD. Thus, bizarre lung cysts may be useful as another novel finding of chronic HDLI in children who have no history of pulmonary infection or other perinatal disorder such as hyaline membrane disease or other interstitial lung disease.

Characteristics of a new respiratory syndrome associated with the use of a humidifier disinfectant: humidifier disinfectant-related respiratory syndrome (HDRS).

OBJECTIVES: The purpose of this study was to characterize a new respiratory syndrome associated with exposure to a humidifier disinfectant (HD) in South Korea that is distinct from the well-known HD-related lung injury (HDLI). The authors identified this condition in 24 study subjects who were family members of patients with definite or probable HDLI (referred to as index cases), and were exposed to HD in the same room as the index cases. MATERIAL AND METHODS: The authors reviewed medical records of 236 family members in 110 families who were exposed to HD in the same rooms and residences as the index cases. RESULTS: They identified 24 family members who were exposed to HD in the same rooms and residences as the index cases, and who developed respiratory disorders that were distinct from HDLI. The clinical signs and symptoms of these individuals were in the upper respiratory tract, such as allergic rhinitis and croup, or in the lower respiratory tract, such as bronchitis and pneumonia. The diffusing capacity of the lung fordetermicarbon monoxide was reduced in 9 of 12 children (data not available for 1 child), and in 4 of 5 adults (data not available for 6 adults). The percent forced vital capacity and forced expiratory volume in one second/forced vital capacity ratios were within the normal ranges in most patients. The computed tomography findings, which mostly indicated non-specific inflammation, were inconsistent with the radiological diagnostic criteria for HDLI, but were abnormal in 8 of 11 adults, and in 2 of 13 children. CONCLUSIONS: The authors propose a new condition, i.e., HD-related respiratory syndrome (HDRS), which is characterized by mild to moderate or atypical respiratory symptoms and signs, and is related to HD exposure, but is distinct from HDLI. The recognition of HDRS may provide a basis for understanding the natural history of HD-related respiratory problems, and for capturing the whole spectrum of HD-related clinical manifestations in the respiratory tract. Int J Occup Med Environ Health. 2020;33(6):829-39.

A Case Report of a Middle East Respiratory Syndrome Survivor with Kidney Biopsy Results.

A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications.

Nationwide Study of Humidifier Disinfectant Lung Injury in South Korea, 1994-2011. Incidence and Dose-Response Relationships.

RATIONALE: Humidifier disinfectant lung injury is an acute lung disease attributed to recurrent inhalation of certain disinfectant aerosols emitted from room humidifiers. An outbreak of this toxic lung injury occurred in South Korea from 1995 until all humidifier disinfectant products were recalled from the consumer market by the government in 2011. OBJECTIVES: A nationwide study was conducted to ascertain and classify all potential cases of humidifier disinfectant lung injury in Korea and to assess dose-response relationships. METHODS: By several mechanisms, clinicians and the general public were invited to report all suspected cases of humidifier disinfectant lung injury to public health officials in South Korea. A committee was convened to define diagnostic criteria based on pathologic, radiologic, and clinical findings for index cases, combined with assessment of environmental exposure to humidifier disinfectants. Clinical review and environmental assessments were performed and later combined to determine overall likelihood of disease for each study participant, classified as definite, probable, possible, or unlikely. Survival time from exposure to onset of symptoms was analyzed to assess dose-response relationships. Three broad categories of risk factors were examined: (1) biological susceptibility, (2) temporal cycle of exposure and recovery, and (3) spatial conditions and density of disinfectant. MEASUREMENTS AND MAIN RESULTS: Of 374 possible cases identified and reviewed, 329 were unanimously classified by the diagnostic committee, as follows: 117 definite, 34 probable, 38 possible and 140 unlikely cases. A total of 62 individuals with definite or probable disease died. Risk factors examined for polyhexamethyleneguanidine phosphate exposure that were found to be significant in shortening survival included age 4 years or younger at onset, use of disinfectant for 7 days per week, airborne density of 800 µg/m(3) or more of disinfectant, and daily exposure 11 or more hours in duration. CONCLUSIONS: Dose-response analysis indicated that development of humidifier disinfectant lung injury and death were associated strongly with recurrent, intense, acute exposure without sufficient recovery time between exposures, more so than long-term cumulative exposure. These findings may explain some reversible or clinically unapparent cases among coexposed family members.

Immune parameters differentiating active from latent tuberculosis infection in humans.

Tuberculosis remains a highly prevalent infectious disease worldwide. Identification of the immune parameters that differentiate active disease from latent infection will facilitate the development of efficient control measures as well as new diagnostic modalities for tuberculosis. Here, we investigated the cytokine production profiles of monocytes and CD4(+) T lymphocytes upon encountering mycobacterial antigens. In addition, cytokines and lipid mediators with immune-modulating activities were examined in plasma samples ex vivo. Comparison of these parameters in active tuberculosis patients and healthy subjects with latent infection revealed that, active tuberculosis was associated with diminished Th1-type cytokine secretion from CD4(+) T cells and less augmented inflammatory cytokine secretion from monocytes induced by IFN-γ than that in latent tuberculosis infection. In addition, a higher plasma concentration of lipoxin A4 and lower ratio of prostaglandin E2 to lipoxin A4 were observed in active cases than in latent infections. These findings have implications for preparing new therapeutic strategies and for differential diagnosis of the two types of tuberculosis infection.

Pulmonary cryptococcosis that mimicked rheumatoid nodule in rheumatoid arthritis lesion.

Recently, the incidence of pulmonary cryptococcosis is gradually increasing in rheumatoid arthritis (RA) patients. Pulmonary rheumatoid nodules (PRN) are rare manifestations of RA. Eighteen months ago, a 65-year old woman was admitted to hospital due to multiple nodules (2.5×2.1×2 cm) with cavitations in the right lower lobe. She was diagnosed with RA three year ago. She had been taking methotrexate, leflunomide, and triamcinolone. A video-assisted thoracoscopic surgery biopsy was performed and PRN was diagnosed. However, a newly growing huge opacity with cavitation was detected in the same site. Pulmonary cryptococcal infection was diagnosed through a transthoracic computed tomograpy guided needle biopsy. Cryptococcus antigen was detected in serum but not in cerebrospinal fluid. The patient was treated with oral fluconazole which resulted clinical improvement and regression of the nodule on a series of radiography. Herein, we report the case of pulmonary cryptococcosis occurring in the same location as that of the PRN.

A case of asymptomatic, localized, and idiopathic diffuse alveolar damage.

Diffuse alveolar damage (DAD) is a histological change in lung tissue, and is generally caused by an acute lung injury, which is characterized by bilateral and widespread damages. Localized DAD occurs very rarely. The causes for DAD are numerous, but the chief cause is acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia, in cases of idiopathic manifestation. The 82-year-old patient, in this case study, showed a DAD lesion in only 1 lobe. The patient was otherwise healthy, with no previous symptoms of DAD. He was admitted to our medical center owing to localized infiltration, observed on his chest radiograph. Laboratory studies showed no signs of infections. DAD was confirmed by a surgical lung biopsy. The patient received corticosteroid treatment and had gradually improved. We report the case of a patient with localized, idiopathic DAD that cannot be classified as acute interstitial pneumonia or acute exacerbation of idiopathic interstitial pneumonia.

Lack of association between the microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene and bronchiectasis among Koreans.

BACKGROUND AND OBJECTIVE: The genetic factors for the development of bronchiectasis are not well understood in most patients. The aim of this study was to elucidate the possible association between bronchiectasis and guanine-thymine (GT) repeat polymorphism in intron 2 of the human Toll-like receptor 2 (TLR2), which has a crucial role in adaptive as well as innate immunity. METHODS: A total of 194 patients with bronchiectasis and the same number of age- and gender-matched healthy blood donors were prospectively enrolled. The numbers of GT repeats were determined by PCR and gene scans. For further analysis, the alleles were classified into three subclasses: 12-16 GT repeats, short alleles (S allele); 17-22 repeats, medium-length alleles (M allele); and 23-27 repeats, long alleles (L allele). RESULTS: The overall distribution of alleles was not different between patient and control groups (P = 0.71). In addition, the frequencies of genotypes including short alleles were not different between patient and control groups (P = 0.92). Extent of bronchiectasis (P = 0.92) and bacterial colonization (P = 0.48) were not associated with any subclass genotype. CONCLUSIONS: Alleles and genotype including the shorter GT repeats in intron 2 of the TLR2, were not associated with the development, extent and bacterial colonization of bronchiectasis in Koreans.