Revised Korean Cough Guidelines, 2020: Recommendations and Summary Statements / 결핵및호흡기질환

Cough is the most common respiratory symptom that can have various causes. It is a major clinical problem that can reduce a patient’s quality of life. Thus, clinical guidelines for the treatment of cough were established in 2014 by the cough guideline committee under the Korean Academy of Tuberculosis and Respiratory Diseases. From October 2018 to July 2020, cough guidelines were revised by members of the committee based on the first guidelines. The purpose of these guidelines is to help clinicians efficiently diagnose and treat patients with cough. This article highlights the recommendations and summary of the revised Korean cough guidelines. It includes a revised algorithm for the evaluation of acute, subacute, and chronic cough. For a chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered in differential diagnoses. If UACS is suspected, first-generation antihistamines and nasal decongestants can be used empirically. In cases with CVA, inhaled corticosteroids are recommended to improve cough. In patients with suspected chronic cough due to symptomatic GERD, proton pump inhibitors are recommended. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, intake of angiotensin-converting enzyme inhibitor, intake of dipeptidyl peptidase-4 inhibitor, habitual cough, psychogenic cough, interstitial lung disease, environmental and occupational factors, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and unexplained cough can also be considered as causes of a chronic cough. Chronic cough due to laryngeal dysfunction syndrome has been newly added to the guidelines.

Revised Korean Cough Guidelines, 2020: Recommendations and Summary Statements / 결핵및호흡기질환

Cough is the most common respiratory symptom that can have various causes. It is a major clinical problem that can reduce a patient’s quality of life. Thus, clinical guidelines for the treatment of cough were established in 2014 by the cough guideline committee under the Korean Academy of Tuberculosis and Respiratory Diseases. From October 2018 to July 2020, cough guidelines were revised by members of the committee based on the first guidelines. The purpose of these guidelines is to help clinicians efficiently diagnose and treat patients with cough. This article highlights the recommendations and summary of the revised Korean cough guidelines. It includes a revised algorithm for the evaluation of acute, subacute, and chronic cough. For a chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered in differential diagnoses. If UACS is suspected, first-generation antihistamines and nasal decongestants can be used empirically. In cases with CVA, inhaled corticosteroids are recommended to improve cough. In patients with suspected chronic cough due to symptomatic GERD, proton pump inhibitors are recommended. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, intake of angiotensin-converting enzyme inhibitor, intake of dipeptidyl peptidase-4 inhibitor, habitual cough, psychogenic cough, interstitial lung disease, environmental and occupational factors, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and unexplained cough can also be considered as causes of a chronic cough. Chronic cough due to laryngeal dysfunction syndrome has been newly added to the guidelines.

Clinical Characteristics of Chronic Cough in Korea / 결핵및호흡기질환

BACKGROUND@#Chronic cough is defined as a cough lasting more than 8 weeks and socio-economic burden of chronic cough is enormous. The characteristics of chronic cough in Korea are not well understood. The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) published guidelines on cough management in 2014. The current study evaluated the clinical characteristics of chronic cough in Korea and the efficacy of the KATRD guidelines.@*METHODS@#This was a multi-center, retrospective observational study conducted in Korea. The participants were over 18 years of age. They had coughs lasting more than 8 weeks. Subjects with current pulmonary diseases, smokers, ex-smokers with more than 10 pack-years or who quit within the past 1 year, pregnant women, and users of cough-inducing medications were excluded. Evaluation and management of cough followed the KATRD cough-management guidelines.@*RESULTS@#Participants with chronic cough in Korea showed age in the late forties and cough duration of more than 1 year. Upper airway cough syndrome was the most common cause of cough, followed by cough-variant asthma (CVA). Gastro-esophageal reflux diseases and eosinophilic bronchitis were less frequently observed. Following the KATRD cough-management guidelines, 91.2% of the subjects improved after 4 weeks of treatment. Responders were younger, had a longer duration of cough, and an initial impression of CVA. In univariate and multivariate analyses, an initial impression of CVA was the only factor related to better treatment response.@*CONCLUSION@#The causes of chronic cough in Korea differed from those reported in other countries. The current Korean guidelines proved efficient for treating Korean patients with chronic cough.

Clinical Characteristics of Chronic Cough in Korea / 결핵및호흡기질환

BACKGROUND@#Chronic cough is defined as a cough lasting more than 8 weeks and socio-economic burden of chronic cough is enormous. The characteristics of chronic cough in Korea are not well understood. The Korean Academy of Tuberculosis and Respiratory Diseases (KATRD) published guidelines on cough management in 2014. The current study evaluated the clinical characteristics of chronic cough in Korea and the efficacy of the KATRD guidelines.@*METHODS@#This was a multi-center, retrospective observational study conducted in Korea. The participants were over 18 years of age. They had coughs lasting more than 8 weeks. Subjects with current pulmonary diseases, smokers, ex-smokers with more than 10 pack-years or who quit within the past 1 year, pregnant women, and users of cough-inducing medications were excluded. Evaluation and management of cough followed the KATRD cough-management guidelines.@*RESULTS@#Participants with chronic cough in Korea showed age in the late forties and cough duration of more than 1 year. Upper airway cough syndrome was the most common cause of cough, followed by cough-variant asthma (CVA). Gastro-esophageal reflux diseases and eosinophilic bronchitis were less frequently observed. Following the KATRD cough-management guidelines, 91.2% of the subjects improved after 4 weeks of treatment. Responders were younger, had a longer duration of cough, and an initial impression of CVA. In univariate and multivariate analyses, an initial impression of CVA was the only factor related to better treatment response.@*CONCLUSION@#The causes of chronic cough in Korea differed from those reported in other countries. The current Korean guidelines proved efficient for treating Korean patients with chronic cough.

Clinical Characteristics of Chronic Cough in Korea / 결핵

Development of Prediction Equation of Diffusing Capacity of Lung for Koreans / 결핵및호흡기질환

BACKGROUND@#The diffusing capacity of the lung is influenced by multiple factors such as age, sex, height, weight, ethnicity and smoking status. Although a prediction equation for the diffusing capacity of Korea was proposed in the mid-1980s, this equation is not used currently. The aim of this study was to develop a new prediction equation for the diffusing capacity for Koreans.@*METHODS@#Using the data of the Korean National Health and Nutrition Examination Survey, a total of 140 nonsmokers with normal chest X-rays were enrolled in this study.@*RESULTS@#Using linear regression analysis, a new predicting equation for diffusing capacity was developed. For men, the following new equations were developed: carbon monoxide diffusing capacity (DLco)=−10.4433−0.1434×age (year)+0.2482×heights (cm); DLco/alveolar volume (VA)=6.01507−0.02374×age (year)−0.00233×heights (cm). For women the prediction equations were described as followed: DLco=−12.8895−0.0532×age (year)+0.2145×heights (cm) and DLco/VA=7.69516−0.02219×age (year)−0.01377×heights (cm). All equations were internally validated by k-fold cross validation method.@*CONCLUSION@#In this study, we developed new prediction equations for the diffusing capacity of the lungs of Koreans. A further study is needed to validate the new predicting equation for diffusing capacity.

Development of Prediction Equation of Diffusing Capacity of Lung for Koreans / 결핵

BACKGROUND: The diffusing capacity of the lung is influenced by multiple factors such as age, sex, height, weight, ethnicity and smoking status. Although a prediction equation for the diffusing capacity of Korea was proposed in the mid-1980s, this equation is not used currently. The aim of this study was to develop a new prediction equation for the diffusing capacity for Koreans. METHODS: Using the data of the Korean National Health and Nutrition Examination Survey, a total of 140 nonsmokers with normal chest X-rays were enrolled in this study. RESULTS: Using linear regression analysis, a new predicting equation for diffusing capacity was developed. For men, the following new equations were developed: carbon monoxide diffusing capacity (DLco)=−10.4433−0.1434×age (year)+0.2482×heights (cm); DLco/alveolar volume (VA)=6.01507−0.02374×age (year)−0.00233×heights (cm). For women the prediction equations were described as followed: DLco=−12.8895−0.0532×age (year)+0.2145×heights (cm) and DLco/VA=7.69516−0.02219×age (year)−0.01377×heights (cm). All equations were internally validated by k-fold cross validation method. CONCLUSION: In this study, we developed new prediction equations for the diffusing capacity of the lungs of Koreans. A further study is needed to validate the new predicting equation for diffusing capacity.

The Korean Cough Guideline: Recommendation and Summary Statement / 결핵및호흡기질환

Cough is one of the most common symptom of many respiratory diseases. The Korean Academy of Tuberculosis and Respiratory Diseases organized cough guideline committee and cough guideline was developed by this committee. The purpose of this guideline is to help clinicians to diagnose correctly and treat efficiently patients with cough. In this article, we have stated recommendation and summary of Korean cough guideline. We also provided algorithm for acute, subacute, and chronic cough. For chronic cough, upper airway cough syndrome (UACS), cough variant asthma (CVA), and gastroesophageal reflux disease (GERD) should be considered. If UACS is suspicious, first generation anti-histamine and nasal decongestant can be used empirically. In CVA, inhaled corticosteroid is recommended in order to improve cough. In GERD, proton pump inhibitor is recommended in order to improve cough. Chronic bronchitis, bronchiectasis, bronchiolitis, lung cancer, aspiration, angiotensin converting enzyme inhibitor, habit, psychogenic cough, interstitial lung disease, environmental and occupational factor, tuberculosis, obstructive sleep apnea, peritoneal dialysis, and idiopathic cough can be also considered as cause of chronic cough. Level of evidence for treatment is mostly low. Thus, in this guideline, many recommendations are based on expert opinion. Further study regarding treatment for cough is mandatory.

Vitamin D Inhibits Expression and Activity of Matrix Metalloproteinase in Human Lung Fibroblasts (HFL-1) Cells / 결핵및호흡기질환

BACKGROUND: Low levels of serum vitamin D is associated with several lung diseases. The production and activation of matrix metalloproteinases (MMPs) may play an important role in the pathogenesis of emphysema. The aim of the current study therefore is to investigate if vitamin D modulates the expression and activation of MMP-2 and MMP-9 in human lung fibroblasts (HFL-1) cells. METHODS: HFL-1 cells were cast into three-dimensional collagen gels and stimulated with or without interleukin-1beta (IL-1beta) in the presence or absence of 100 nM 25-hydroxyvitamin D (25(OH)D) or 1,25-dihydroxyvitamin D (1,25(OH)2D) for 48 hours. Trypsin was then added into the culture medium in order to activate MMPs. To investigate the activity of MMP-2 and MMP-9, gelatin zymography was performed. The expression of the tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) was measured by enzyme-linked immunosorbent assay. Expression of MMP-9 mRNA and TIMP-1, TIMP-2 mRNA was quantified by real time reverse transcription polymerase chain reaction. RESULTS: IL-1beta significantly stimulated MMP-9 production and mRNA expression. Trypsin converted latent MMP-2 and MMP-9 into their active forms of MMP-2 (66 kDa) and MMP-9 (82 kDa) within 24 hours. This conversion was significantly inhibited by 25(OH)D (100 nM) and 1,25(OH)2D (100 nM). The expression of MMP-9 mRNA was also significantly inhibited by 25(OH)D and 1,25(OH)2D. CONCLUSION: Vitamin D, 25(OH)D, and 1,25(OH)2D play a role in regulating human lung fibroblast functions in wound repair and tissue remodeling through not only inhibiting IL-1beta stimulated MMP-9 production and conversion to its active form but also inhibiting IL-1beta inhibition on TIMP-1 and TIMP-2 production.

Epidemiological Aspects of Pertussis among Adults and Adolescents in a Korean Outpatient Setting: A Multicenter, PCR-Based Study

Epidemiological data of Bordetella pertussis infection among adolescents and adults are limited in Korea. Patients (> or = 11 yr of age) with a bothersome cough for less than 30 days were enrolled during a 1-yr period at 22 hospitals in Korea. Nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and for bacteriologic culture. In total, 490 patients were finally enrolled, and 34 (6.9%) patients tested positive for B. pertussis; cough duration (14.0 days [7.0-21.0 days]) and age distribution were diverse. The incidence was the highest in secondary referral hospitals, compared to primary care clinics or tertiary referral hospitals (24/226 [10.6%] vs. 3/88 [3.4%] vs. 7/176 [4.0%], P = 0.012), and the peak incidence was observed in February and August (15.8% and 15.9%), with no confirmed cases between March and June. In the multivariate analysis, post-tussive vomiting was significantly associated with pertussis (odds ratio, 2.508; 95% confidence interval, 1.146-5.486) and secondary referral hospital showed a borderline significance. In conclusion, using a PCR-based method, 6.9% of adolescent and adult patients with an acute cough illness had pertussis infection in an outpatient setting. However, hospital levels and seasonal trends must be taken into account to develop a better strategy for controlling pertussis.

A Multicenter Study of Pertussis Infection in Adults with Coughing in Korea: PCR-Based Study / 결핵및호흡기질환

BACKGROUND: Limited data on the incidence and clinical characteristics of adult pertussis infections are available in Korea. METHODS: Thirty-one hospitals and the Korean Centers for Disease Control and Prevention collaborated to investigate the incidence and clinical characteristics of pertussis infections among adults with a bothersome cough in non-outbreak, ordinary outpatient settings. Nasopharyngeal aspirates or nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and culture tests. RESULTS: The study enrolled 934 patients between September 2009 and April 2011. Five patients were diagnosed as confirmed cases, satisfying both clinical and laboratory criteria (five positive PCR and one concurrent positive culture). Among 607 patients with cough duration of at least 2 weeks, 504 satisfied the clinical criteria of the US Centers for Disease Control and Prevention (i.e., probable case). The clinical pertussis cases (i.e., both probable and confirmed cases) had a wide age distribution (45.7+/-15.5 years) and cough duration (median, 30 days; interquartile range, 18.0~50.0 days). In addition, sputum, rhinorrhea, and myalgia were less common and dyspnea was more common in the clinical cases, compared to the others (p=0.037, p=0.006, p=0.005, and p=0.030, respectively). CONCLUSION: The positive rate of pertussis infection may be low in non-outbreak, ordinary clinical settings if a PCR-based method is used. However, further prospective, well-designed, multicenter studies are needed.

Simvastatin as a Modulator of Tissue Remodeling through Inhibition of Matrix Metalloproteinase (MMP) Release from Human Lung Fibroblasts / 결핵및호흡기질환

BACKGROUND: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. METHODS: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-alpha, TNF-a and interleukin-1beta, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. RESULTS: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. CONCLUSION: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.

A Case of Pulmonary Capillary Hemangiomatosis-Like Lesion Followed for Seven Years / 결핵및호흡기질환

Pulmonary capillary hemangiomatosis (PCH) is a rare disease of unknown etiology that is characterized by nodules composed of infiltrating capillary blood vessels. Herein, we describe a case of a PCH-like lesion that was detected by chest computed tomography. Transthoracic needle aspiration resulted in life-threatening hemorrhage. The patient was followed for seven years. He remained in good health and a follow up image showed little interval change.

Proposal of New Criteria for Assessing Respiratory Impairment / 결핵및호흡기질환

Social welfare services for respiratory-disabled persons in Korea are offered based on the respiratory impairment grade, which is determined by 3 clinical parameters; dyspnea, forced expiratory volume in 1 second (FEV1), and arterial oxygen tension. This grading system has several limitations in the objective assessment of respiratory impairment. We reviewed several guidelines for the evaluation of respiratory impairment and relevant articles. Then, we discussed a new grading system with respiratory physicians. Both researchers and respiratory physicians agreed that pulmonary function tests are essential in assessing the severity of respiratory impairment, forced vital capacity (FVC), FEV1 and single breath diffusing capacity (DLco) are the primarily recommended tests. In addition, we agreed that arterial blood gas analysis should be reserved for selected patients. In conclusion, we propose a new respiratory impairment grading system utilizing a combination FVC, FEV1 and DLco scores, with more social discussion included.

Early Diagnosis and Management of Chronic Obstructive Pulmonary Disease / 결핵및호흡기질환

Chronic obstructive pulmonary disease (COPD) is a substantially under-diagnosed disorder, and the diagnosis is usually delayed until the disease is advanced. However, the benefit of early diagnosis is not yet clear, and there are no guidelines in Korea for doing early diagnosis. This review highlights several issues regarding early diagnosis of COPD. On the basis of several lines of evidence, early diagnosis seems quite necessary and beneficial to patients. Early diagnosis can be approached by several methods, but it should be confirmed by quality-controlled spirometry. Compared with its potential benefit, the adverse effects of spirometry or pharmacotherapy appear relatively small. Although it is difficult to evaluate the benefit of early diagnosis by well-designed trials, several lines of evidence suggest that we should try to diagnose and manage patients with COPD at early stages of the disease.

New Paradigms in the Pathogenesis of Chronic Obstructive Pulmonary Disease / 결핵및호흡기질환

A key mechanism in the pathogenesis of chronic obstructive pulmonary disease is thought to be an abnormal inflammatory response in the lungs to the inhalation of toxic particles and gases, derived from tobacco smoke, air pollution, and/or occupational exposures. This review highlights the potential participation of several alternative pathogenetic processes, particularly involving the potential participation of biological and pathobiological processes related to aging, including oxidative stress and enhanced expression of markers of senescence/aging in emphysematous lungs, and the potential for enhanced tissue destruction involving alveolar cell apoptosis.

Induction of Autophagy by Low Dose of Cisplatin in H460 Lung Cancer Cells / 결핵및호흡기질환

BACKGROUND: Most lung cancer patients receive systemic chemotherapy at an advanced stage disease. Cisplatin-based chemotherapy is the main regimen for treating advanced lung cancer. Recently, autophagy has become an important mechanism of cellular adaptation under starvation or cell oxidative stress. The purpose of this study was to determine whether or not autophagy can occurred in cisplatin-treated lung cancer cells. METHODS: H460 cells were incubated with RPMI 1640 and treated in 5 micrometer or 20 micrometer cisplatin concentrations at specific time intervals. Cells surviving cisplatin treatment were measured and compared using an MTT cell viability assay to cells that underwent apoptosis with autophagy by nuclear staining, apoptotic or autophagic related proteins, and autophagic vacuoles. The development of acidic vascular organelles was using acridine orange staining and fluorescent expression of GFP-LC3 protein in its transfected cells was observed to evaluate autophagy. RESULTS: Lung cancer cells treated with 5 micrometer cisplatin-treated were less sensitive to cell death than 20 micrometer cisplatin-treated cells in a time-dependent manner. Nuclear fragmentation at 5 micrometer was not detected, even though it was discovered at 20 micrometer. Poly (ADP-ribose) polymerase cleavages were not detected in 5 micrometer within 24 hours. Massive vacuolization in the cytoplasm of 5 micrometer treated cells were observed. Acridine orange stain-positive cells was increased according in time-dependence manner. The autophagosome-incorporated LC3 II protein expression was increased in 5 micrometer treated cells, but was not detected in 20 micrometer treated cells. The expression of GFP-LC3 were increased in 5 micrometer treated cells in a time-dependent manner. CONCLUSION: The induction of autophagy occurred in 5 micrometer dose of cisplatin-treated lung cancer cells.

Induction of Autophagy by Low Dose of Cisplatin in H460 Lung Cancer Cells / 결핵및호흡기질환

BACKGROUND: Most lung cancer patients receive systemic chemotherapy at an advanced stage disease. Cisplatin-based chemotherapy is the main regimen for treating advanced lung cancer. Recently, autophagy has become an important mechanism of cellular adaptation under starvation or cell oxidative stress. The purpose of this study was to determine whether or not autophagy can occurred in cisplatin-treated lung cancer cells. METHODS: H460 cells were incubated with RPMI 1640 and treated in 5 micrometer or 20 micrometer cisplatin concentrations at specific time intervals. Cells surviving cisplatin treatment were measured and compared using an MTT cell viability assay to cells that underwent apoptosis with autophagy by nuclear staining, apoptotic or autophagic related proteins, and autophagic vacuoles. The development of acidic vascular organelles was using acridine orange staining and fluorescent expression of GFP-LC3 protein in its transfected cells was observed to evaluate autophagy. RESULTS: Lung cancer cells treated with 5 micrometer cisplatin-treated were less sensitive to cell death than 20 micrometer cisplatin-treated cells in a time-dependent manner. Nuclear fragmentation at 5 micrometer was not detected, even though it was discovered at 20 micrometer. Poly (ADP-ribose) polymerase cleavages were not detected in 5 micrometer within 24 hours. Massive vacuolization in the cytoplasm of 5 micrometer treated cells were observed. Acridine orange stain-positive cells was increased according in time-dependence manner. The autophagosome-incorporated LC3 II protein expression was increased in 5 micrometer treated cells, but was not detected in 20 micrometer treated cells. The expression of GFP-LC3 were increased in 5 micrometer treated cells in a time-dependent manner. CONCLUSION: The induction of autophagy occurred in 5 micrometer dose of cisplatin-treated lung cancer cells.

The Effect of Autophagy to Cell Death in Nutrient-Deprived H460 Cells / 결핵및호흡기질환

BACKGROUND: Autophagy is an important adaptive mechanism in normal development and in response to changing environmental stimuli in cancer. Previous papers have reported that different types of cancer underwent autophagy to obtain amino acids as energy source of dying cells in nutrient-deprived conditions. However, whether or not autophagy in the process of lung cancer causes death or survival is controversial. Therefore in this study, we investigated whether nutrient deprivation induces autophagy in human H460 lung cancer cells. METHODS: H460, lung cancer cells were incubated in RPMI 1640 medium, and the starved media, which are BME and RPMI media without serum, including 2-deoxyl-D-glucose according to time dependence. To evaluate the viability and find out the mechanism of cell death under nutrient-deprived conditions, the MTT assay and flow cytometry were done and analyzed the apoptotic and autophagic related proteins. It is also measured the development of acidic vascular organelles by acridine orange. RESULTS: The nutrient-deprived cancer cell is relatively sensitive to cell death rather than normal nutrition. Massive cytoplasmic vacuolization was seen under nutrient-deprived conditions. Autophagic vacuoles were visible at approximately 12 h and as time ran out, vacuoles became larger and denser with the increasing number of vacuoles. In addition, the proportion of acridine orange stain-positive cells increased according to time dependence. Localization of GFP-LC3 in cytoplasm and expression of LC-3II and Beclin 1 were increased according to time dependence on nutrient-deprived cells. CONCLUSION: Nutrient deprivation induces cell death through autophagy in H460 lung cancer cells.

A Case Report of Usual Interstitial Pneumonia after Treatment of Bronchopneumonia / 가정의학회지

Usual interstitial pneumonia (UIP) is one type of idiopathic interstitial pneumonia, characterized by its poor prognosis and gradual deterioration of clinical course. So it is important to distinguish UIP from other interstitial pneumonia. Defi nitive histological diagnosis of UIP requires lung biopsy. The criteria for diagnosis of UIP in the absence of a surgical lung biopsy were recently defi ned. We report a case of 75-year-old man who was diagnosed as bronchopneumonia with chief complaint of fever, dyspnea on fi rst visit, then fi nally diagnosed as UIP through the remaining of chest abnormality after treatment.