Multicenter Adherence Study of Asthma Medication for Children in Korea

김창근,Zak Callaway,최준기,김효빈,권은미,장윤석,나영호,홍수종,오재원,김현희,임대현,김성원,박강서,조용훈,정해리,박희주,정상근,강임주,현명철,오무영,정진아,김명성,심정연,김진택,고영율 대한천식알레르기학회 2019 Allergy, Asthma & Immunology Research Vol.11 No.2

Purpose: Adherence is a major component of successful medical treatment. However, non-adherence remains a barrier to effective delivery of healthcare worldwide. Methods: Twenty healthcare facilities (secondary or tertiary hospitals) belonging to the Korean Academy of Pediatric Allergy and Respiratory Diseases (KAPARD) participated. Questionnaires were given to patients currently receiving treatment in the form of inhalant useor oral intake or transdermal patch for mild to moderate asthma. Results: A total of 1,838 patients responded to the questionnaire. Mean age was 5.98 ± 3.79 years (range: 0-18 years). With help from their caregivers, the percentage of patients that answered “taking as prescribed” was 38.04% for inhalant users, 50.09% for oral medication users and 67.42% for transdermal users. Transdermal patch users had significantly greater adherence compared to the other 2 groups (P < 0.001). The 34.15% of inhalant users, 70.33% of oral medication users and 93.00% of transdermal patch users felt that their medication delivery system was “Easy” or “Very easy” to use (P < 0.001). “Method of administration” was deemed to be the most difficult part of the treatment regimen to follow, and 76.7% of patients preferred once-daily administration (i.e., “Frequency of administration”). Conclusions: Asthma medication adherence in young children was found to be better in the transdermal patch group. This may be due to requiring fewer doses and easy to follow instructions. From an adherence point of view, the transdermal patch seems more useful for long-term asthma control in children compared to oral or inhaled medicine.

Montelukast Reduces Serum Levels of Eosinophil-Derived Neurotoxin in Preschool Asthma

김창근,Zak Callaway,박진성,Hisashi Nishimori,Tikatoshi Ogino,Mizuho Nagao,다카오후지사와 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.6

Purpose: Several markers for eosinophilic inflammation have been proposed to predictresponse to asthma treatment. However, definitive criteria for treatment decisions have notyet been established. We investigate a potentially useful relatively non-invasive biomarker,eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide ormontelukast, common treatment for children with asthma. Methods: Young children (1 to 6 years old) were enrolled in this randomized, parallel,2-group, open-label trial. Criteria for eligibility included: 1) being symptomatic during therun-in period; and 2) having a serum EDN (sEDN) level ≥ 53 ng/mL, with positive specificimmunoglobulin E to house dust mite. Eligible patients were randomly placed into 2 groups:the BIS group received budesonide inhalation suspension (BIS) 0.5 mg once daily; the MONTgroup received montelukast 4 mg once daily. Ineligible patients were invited to receivemontelukast 4 mg once daily (OBS group). Treatment period was 12 weeks. Results: Asthma control days increased significantly in the BIS and MONT groups (P < 0.000)over the 12-week study period. There was no significant change in sEDN in the BIS group butthere was a significant decrease in the MONT group (P < 0.000). Patients in the OBS groupwith high EDN levels (> 53 ng/mL) showed a significant decrease due to MONT treatment(P = 0.023). Rescue medication usage significantly decreased in the BIS and MONT groups(P < 0.000). Conclusions: EDN is a useful relatively non-invasive biomarker for predicting responses tomontelukast and budesonide treatment of preschool children with beta2-agonist responsiverecurrent wheeze and multiple-trigger wheeze (Trial registry at UMIN Clinical Trials Registry,UMIN000008335).

Viral Infections and Associated Factors That Promote Acute Exacerbations of Asthma

김창근,Zak Callaway,James E. Gern 대한천식알레르기학회 2018 Allergy, Asthma & Immunology Research Vol.10 No.1

Despite asthma being the most common chronic childhood ailment, there is still much to learn about the disease. Early childhood infections with well-known or emerging viruses can lay the pathophysiologic framework for asthma development and exacerbation later in life, which may be due partly to alteration of the airway microbiome. Once asthma is established, acute exacerbations are usually associated with infections with respiratory viruses, such as rhinoviruses (RVs). Once again, there are bidirectional interactions between viruses and airway bacteria that appear to influence the severity of illness and the likelihood of exacerbation. Studies employing recent advances in viral and bacterial identification analytic techniques will clarify these new concepts and may provide the basis for new treatments or prevention or respiratory infection-associated exacerbation. This paper is a review of the associations among respiratory viruses, bacteria, inflammatory mechanisms, and asthma exacerbation.

Clinical and Epidemiological Comparison of Human Metapneumovirus and Respiratory Syncytial Virus in Seoul, Korea, 2003-2008

김창근,최준기,Zak Callaway,김효빈,정주영,고영률,신보문 대한의학회 2010 Journal of Korean medical science Vol.25 No.3

Human metapneumovirus (HMPV) shares clinical and epidemiological characteristics with well-known respiratory syncytial virus (RSV). The aim of this study was to investigate the clinical and epidemiological differences between HMPV- and RSVinduced wheezing illnesses. A total of 1,008 nasopharyngeal aspirate specimens was collected from 1,008 pediatric patients hospitalized with acute respiratory tract infection at Inje University Sanggye Paik Hospital from December 2003 to April 2008,and tested for seven common respiratory viruses. Conditions classified as wheezing illness were bronchiolitis, reactive airways disease, and bronchial asthma. HMPV caused a significantly lower proportion of wheezing illness when compared to RSV (48.1% vs. 82.2%, P<0.05). HMPV-induced wheezing illness occurred predominantly in older patients when compared to RSV patients (P<0.001). RSV infections peaked in the fall and winter followed by peaks of HMPV infection in winter and spring. Eosinophil counts were significantly higher (P<0.01) in RSV patients when compared to HMPV patients. These results show that human metapneumovirus patients exhibit several different clinical and epidemiological characteristics, such as higher proportion of wheezing illness, age and seasonal incidence, and eosinophil counts,when compared to RSV patients.

Fatal and Near-fatal Cases of Lower Respiratory Tract Infection with Human Rhinovirus Group A

윤정림,최준기,Zak Callaway,김효빈,김창근 대한 소아알레르기 호흡기학회 2010 Allergy Asthma & Respiratory Disease Vol.20 No.1

Human rhinoviruses (HRV) mostly cause mild and self-limiting upper respiratory tract infections. We report 2 infants with acute respiratory failure requiring mechanical ventilation, 1 of whom deteriorated to death. The causal pathogen was HRV group A confirmed by multiplex-PCR. In Korea, this is the first report of severe respiratory failure caused by HRV group A during the same season.

만성 기침 환자의 천식 진단을 위한 호산구 탈과립 단백의 효용성

김예진 ( Ye Jin Kim ),김효빈 ( Hyo Bin Kim ),김창근 ( Chang Keun Kim ),( Zak Callaway ) 대한천식알레르기학회 2010 천식 및 알레르기 Vol.30 No.4

Background: Chronic cough is a common non-specific symptom and has various causes including asthma. Objective: The aims of this study were to compare eosinophilic degranulation in the airways between chronic cough patients with and without asthma and to evaluate correlations between sputum eosinophils and eosinophilic degranulation proteins. Method: Thirty-seven patients with chronic cough and 9 normal individuals (control group) were enrolled. Patients with chronic cough were divided into 2 groups based on positivity for bronchial hyperresponsiveness (BHR): those with asthma (asthma group, n=18) and those without asthma (non-asthma group, n=19). Sputum levels of eosinophil- derived neurotoxin (EDN) and major basic protein (MBP) levels were measured, and eosinophil counts were performed in all patients. Result: Sputum % eosinophils were increased in both the asthma and non-asthma groups compared to the control group. However, sputum EDN/MBP levels were increased only in the asthma group compared to the non-asthma and control groups. Sputum % eosinophils correlated positively with sputum EDN/MBP levels in the asthma group, but not in the Non-asthma group. Conclusion: Increased EDN/MBP levels and significant correlations between % eosinophils and EDN/MBP levels were observed only in the asthma group, suggesting that eosinophil degranulation proteins could be a marker for identifying chronic cough due to asthma. (Korean J Asthma Allergy Clin Immunol 2010;30:293-298)

Quercetin Induces Mitochondrial Biogenesis through Activation of HO-1 in HepG2 Cells

Rayamajhi, Nabin,Kim, Seul-Ki,Go, Hiroe,Joe, Yeonsoo,Callaway, Zak,Kang, Jae-Gu,Ryter, Stefan W.,Chung, Hun Taeg Hindawi Publishing Corporation 2013 Oxidative medicine and cellular longevity Vol.2013 No.-

<P>The regeneration of mitochondria by regulated biogenesis plays an important homeostatic role in cells and tissues and furthermore may provide an adaptive mechanism in certain diseases such as sepsis. The heme oxygenase (HO-1)/carbon monoxide (CO) system is an inducible cytoprotective mechanism in mammalian cells. Natural antioxidants can provide therapeutic benefit, in part, by inducing the HO-1/CO system. This study focused on the mechanism by which the natural antioxidant quercetin can induce mitochondrial biogenesis in HepG2 cells. We found that quercetin treatment induced expression of mitochondrial biogenesis activators (PGC-1<I><I>α</I></I>, NRF-1, TFAM), mitochondrial DNA (mtDNA), and proteins (COX IV) in HepG2 cells. The HO inhibitor SnPP and the CO scavenger hemoglobin reversed the effects of quercetin on mitochondrial biogenesis in HepG2 cells. The stimulatory effects of quercetin on mitochondrial biogenesis could be recapitulated <I>in vivo</I> in liver tissue and antagonized by SnPP. Finally, quercetin conferred an anti-inflammatory effect in the liver of mice treated with LPS and prevented impairment of mitochondrial biogenesis by LPS <I>in vivo</I>. These salutary effects of quercetin <I>in vivo</I> were also antagonized by SnPP. Thus, our results suggest that quercetin enhances mitochondrial biogenesis mainly via the HO-1/CO system <I>in vitro</I> and <I>in vivo</I>. The beneficial effects of quercetin may provide a therapeutic basis in inflammatory diseases and sepsis.</P>

Curcumin protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase-1 expression and reduction of reactive oxygen

Woo, Je Moon,Shin, Da-Yong,Lee, Sung Ju,Joe, Yeonsoo,Zheng, Min,Yim, Jin Ho,Callaway, Zak,Chung, Hun Taeg Molecular Vision 2012 Molecular vision Vol.18 No.-

<P><B>Purpose</B></P><P>To determine whether curcumin induces expression of the defensive enzyme heme oxygenase-1 (HO-1) and protects cells against oxidative stress in cultured human retinal pigment epithelial cells.</P><P><B>Methods</B></P><P>Effective concentrations and toxicities of curcumin were determined after 3 h of curcumin treatment with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Confluent human retinal pigment epithelium cell lines (ARPE-19) were preincubated with curcumin and oxidatively challenged with H<SUB>2</SUB>O<SUB>2</SUB>. HO-1 expression was determined with western blot analysis. To confirm the protective role of HO-1 in oxidative stress, small interfering RNA (siRNA) against HO-1 or inhibitor of HO-1 was treated with curcumin in retinal pigment epithelium cells. Intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry and confocal microscopy. Apoptosis was evaluated with Annexin V-fluoroscein isothiocyanate staining.</P><P><B>Results</B></P><P>Curcumin had little cytotoxicity at concentrations less than 30 μM, and HO-1 expression was the highest at the 15 μM concentration. At this concentration, curcumin also increased the cytoprotective effect against the oxidative stress of H<SUB>2</SUB>O<SUB>2</SUB> through the reduction of ROS levels in human retinal pigment epithelial cells. Curcumin’s effect on the reduction of ROS was mediated by the increase in HO-1 expression.</P><P><B>Conclusions</B></P><P>Curcumin upregulated the oxidative stress defense enzyme HO-1 and may protect human retinal pigment epithelial cells against oxidative stress by reducing ROS levels.</P>

Human Rhinovirus Group A의 치명적인 하기도 감염 증례

윤정림 ( Jung Rim Yoon ),최준기 ( Jun Gi Choi ),김효빈 ( Hyo Bin Kim ),김창근 ( Chang Keun Kim ),( Zak Callaway ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2010 소아알레르기 및 호흡기학회지 Vol.20 No.1

Human rhinoviruses (HRV) 는 성인과 소아에서 상기도 감염의 가장 흔한 바이러스로 알려져 왔다. 최근 HRV의 하기도 감염이나 천식과의 연관성에 대한 연구들이 보고되고 있으며, HRV가 3개월 미만 영아에서 SIDS (sudden infant death syndrome)의 병인 중에 하나로 알려져 있다. 이에 저자들이 경험한 HRV의 치명적인 하기도 감염의 증례 2례를 보고하는 바이다. Human rhinoviruses (HRV) mostly cause mild and self-limiting upper respiratory tract infections. We report 2 infants with acute respiratory failure requiring mechanical ventilation, 1 of whom deteriorated to death. The causal pathogen was HRV group A confirmed by multiplex-PCR. In Korea, this is the first report of severe respiratory failure caused by HRV group A during the same season. [Pediatr Allergy Respir Dis (Korea) 2010;20:76-80]