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Impact Factor

2022 - 2022Available




Latest Articles

Vol.85 No.3

10papers in this issue.

Natasha Cordeiro dos Santos(Department of Life Sciences, State University of Bahia (UNEB), Bahia, Brazil) ; Marc Miravitlles(Department of Pneumology, Hospital Vall d’Hebron/Vall d’Hebron Research institute (VHIR), Barcelona, Spain) ; Aquiles Assunção Camelier(Department of Life Sciences, State University of Bahia (UNEB), Bahia, Brazil) ; Victor Durier Cavalcanti de Almeida(Department of Life Sciences, State University of Bahia (UNEB), Bahia, Brazil) ; Roberto Rodrigues Bandeira Tosta Maciel(Department of Life Sciences, State University of Bahia (UNEB), Bahia, Brazil) ; Fernanda Warken Rosa Camelier(Department of Life Sciences, State University of Bahia (UNEB), Bahia, Brazil) pp.205-220 https://doi.org/10.4046/trd.2021.0179

This study aimed to describe the prevalence of comorbidities associated with chronic obstructive pulmonary disease (COPD) and their relation with relevant outcomes. A systematic review based on the PRISMA methodology was performed from January 2020 until July 2021. The MEDLINE, Lilacs, and Scielo databases were searched to identify studies related to COPD and its comorbidities. Observational studies on the prevalence of comorbidities in COPD patients and costs with health estimates, reduced quality of life, and mortality were included. Studies that were restricted to one or more COPD pain assessments and only specific comorbidities such as osteoporosis, bronchitis, and asthma were excluded. The initial search identified 1,409 studies and after applying the inclusion and exclusion criteria, 20 studies were finally selected for analysis (comprising data from 447,459 COPD subjects). The most frequent COPD comorbidities were: hypertension (range, 17%–64.7%), coronary artery disease (19.9%–47.8%), diabetes (10.2%–45%), osteoarthritis (18%–43.8%), psychiatric conditions (12.1%–33%), and asthma (14.7%–32.5%). Several comorbidities had an impact on the frequency and severity of COPD exacerbations, quality of life, and mortality risk, in particular malignancies, coronary artery disease, chronic heart failure, and cardiac arrhythmias. Comorbidities, especially cardiovascular diseases and diabetes, are frequent in COPD patients, and some of them are associated with higher mortality.


Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation due to chronic airway inflammation and destruction of the alveolar structure from persistent exposure to oxidative stress. The body has various antioxidant mechanisms for efficiently coping with such oxidative stress. The nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) is a representative system. Dysregulation of the Nrf2-ARE pathway is responsible for the development and promotion of COPD. Furthermore, COPD severity is also closely related to this pathway. There has been a clinical impetus to use Nrf2 for diagnostic and therapeutic purposes. Therefore, in this work, we systematically reviewed the clinical significance of Nrf2 in COPD patients, and discuss the value of Nrf2 as a potential COPD biomarker.

Narongwit Nakwan(Hat Yai Hospital, Songkhla) ; Thidarat Ruklerd(Hat Yai Hospital, Songkhla, Thailand) ; Pattarawadee Taptawee(Hat Yai Hospital, Songkhla, Thailand) pp.227-236 https://doi.org/10.4046/trd.2022.0038

Background: The use of low-dose inhaled corticosteroid-formoterol as reliever monotherapy has recently been recommended in the asthma treatment guidelines. However, the efficacy of this treatment strategy has not yet been determined during the stepping-down period in moderate asthma. This study aimed to evaluate the feasibility of reducing treatment to as-needed budesonide-formoterol (BFM) in moderate asthma with complete remission.Methods: We randomly assigned 31 patients (8 males and 23 females with a mean age of 57.2 years) with complete remission of asthma by inhaled BFM (160/4.5 μg) twice daily to receive BFM (160/4.5 μg) as needed (16 patients), or budesonide (BUD) (200 μg) twice daily (15 patients). The study was an open-label study done for 48 weeks, with the primary outcome as the cumulative percentages of patients with treatment failure (asthma exacerbation or loss of asthma control or lack of satisfaction after using medications) in the two groups.Results: Six patients (42%) using as-needed BFM had treatment failure, as compared with three patients (21.4%) using BUD maintenance (hazards ratio for as-needed BFM, 1.77; 95% confidential interval, 0.44–7.12; p=0.41). The changes in forced expiratory volume in 1 second were −211.3 mL with as-needed BFM versus −97.8 mL with BUD maintenance (difference, 113.5 mL; p=0.75) and the change in fractional exhaled nitric oxide was significantly higher in both groups, at 8.68 parts per billion (ppb) in the as-needed BFM group and 2.5 ppb. in the BUD maintenance group (difference, 6.18 ppb; p=0.049).Conclusion: Compared with BUD maintenance, there were no significant differences in treatment failure rate in patients who received as-needed BFM during the stepping down period in moderate asthma. However, they showed reduced lung function and relapsed airway inflammation. The results are limited by imprecision, and further large RCTs are needed.


Background: We evaluated the effect of particulate matter (PM) and cigarette smoke extract (CSE) on bronchial epithelial cell survival, as well as oxidative stress and autophagy levels. Moreover, we aimed to assess the effect of the antioxidant N-acetylcysteine (NAC) on the adverse effects of PM and CSE exposure.Methods: Normal human bronchial epithelial cells (BEAS-2B cells) were exposed to urban PM with or without CSE, after which cytotoxic effects, including oxidative stress and autophagy levels, were measured. After identifying the toxic effects of urban PM and CSE exposure, the effects of NAC treatment on cell damage were evaluated.Results: Urban PM significantly decreased cell viability in a concentration-dependent manner, which was further aggravated by simultaneous treatment with CSE. Notably, pretreatment with NAC at 10 mM for 1 hour reversed the cytotoxic effects of PM and CSE co-exposure. Treatment with 1, 5, and 10 mM NAC was shown to decrease reactive oxygen species levels induced by exposure to both PM and CSE. Additionally, the autophagy response assessed via LC3B expression was increased by PM and CSE exposure, and this also attenuated by NAC treatment.Conclusion: The toxic effects of PM and CSE co-exposure on human bronchial epithelial cells, including decreased cell viability and increased oxidative stress and autophagy levels, could be partly prevented by NAC treatment.

Bo Young Lee(Soonchunhyang University College of Medicine) ; Jang Joonyong(Department of Internal Medicine) ; Kim Ki-Up(Soonchunhyang University College of Medicine) ; Kim Yang-Ki(Soonchunhyang University College of Medicine) ; Uh Soo-Taek ; Jang Gae-Eil(Department of Internal Medicine) ; Wonho Chang(Soonchunhyang University College of Medicine) ; pp.249-255 https://doi.org/10.4046/trd.2022.0004

Background: The main cause of death in pulmonary embolism (PE) is right-heart failure due to acute pressure overload. In this sense, extracorporeal membrane oxygenation (ECMO) might be useful in maintaining hemodynamic stability and improving organ perfusion. Some previous studies have reported ECMO as a bridge to reperfusion therapy of PE. However, little is known about the patients that benefit from ECMO.Methods: Patients who underwent ECMO due to pulmonary thromboembolism at a single university-affiliated hospital between January 2010 and December 2018 were retrospectively reviewed.Results: During the study period, nine patients received ECMO in high-risk PE. The median age of the patients was 60 years (range, 22–76 years), and six (66.7%) were male. All nine patients had cardiac arrests, of which three occurred outside the hospital. All the patients received mechanical support with veno-arterial ECMO, and the median ECMO duration was 1.1 days (range, 0.2–14.0 days). ECMO with anticoagulation alone was performed in six (66.7%), and ECMO with reperfusion therapy was done in three (33.3%). The 30-day mortality rate was 77.8%. The median time taken from the first cardiac arrest to initiation of ECMO was 31 minutes (range, 30–32 minutes) in survivors (n=2) and 65 minutes (range, 33–482 minutes) in non-survivors (n=7).Conclusion: High-risk PE with cardiac arrest has a high mortality rate despite aggressive management with ECMO and reperfusion therapy. Early decision to start ECMO and its rapid initiation might help save those with cardiac arrest in high-risk PE.

Park Sanghee(Clinical Research Center) ; Jung Jihee(Masan National Tuberculosis Hospital, Changwon) ; Kim Jiyeon(Masan National Tuberculosis Hospital, Changwon) ; Han Sang Bong(Department of Laboratory Medicine, Masan National) ; pp.256-263 https://doi.org/10.4046/trd.2021.0175

Background <i>Mycobacterium tuberculosis</i> (Mtb) is resistant to the β-lactam antibiotics due to a non-classical transpeptidase in the cell wall with β-lactamase activity. A recent study showed that meropenem combined with a β-lactamase inhibitor clavulanate, was effective in MDR and XDR tuberculosis (TB). However, clavulanate can only be used in drugs containing amoxicillin in Korea. In this study, we investigated the susceptibility and genetic mutations of drug-resistant Mtb isolates to amoxicillin-clavulanate and meropenem-clavulanate to improve the diagnosis and treatment of drug-resistant TB patients.Methods The minimum inhibitory concentration (MIC) of amoxicillin-clavulanate and meropenem-clavulanate was examined by resazurin microtiter assay. We used 82 MDR and 40 XDR strains isolated in Korea and two reference laboratory strains. Mutations of drug targets <i>blaC, blaI, ldtA, ldtB, dacB2</i>, and <i>crfA</i> were analyzed by PCR and DNA sequencing.Results The MIC<sub>90</sub> values of amoxicillin and meropenem with clavulanate in drug-resistant Mtb isolates were 64 and 16, respectively. Gene mutations related to amoxicillin/clavulanate and meropenem/clavulanate resistance could not be identified, but T448G mutation of was found in the <i>blaC</i> gene related to β-lactam antibiotics high susceptibility.Conclusion Our results provide clinical consideration of β-lactams in treating drug-resistant TB and potential molecular markers of amoxicillin-clavulanate and meropenem-clavulanate susceptibility.

Eum Seok-Yong(International Tuberculosis Research Center) ; Baek Seung-Hun(Yonsei University College of Medicine) ; Hong Min-Sun(Yonsei University College of Medicine) ; Lee Jong-Seok(International Tuberculosis Research Center) ; Cho Eun-Jin(International Tuberculosis Research Center) ; Lee Ji-Im(International Tuberculosis Research Center) ; Cho Sang-Nae(Yonsei University College of Medicine) ; Sun-Kyoung Lee(International Tuberculosis Research Center) pp.264-272 https://doi.org/10.4046/trd.2021.0134

Background: The current conventional drug susceptibility test (DST) for <i>Mycobacterium tuberculosis</i> (Mtb) takes several weeks of incubation to obtain results. As a rapid method, molecular DST requires only a few days to get the results but does not fully cover the phenotypic resistance. A new rapid method based on the ability of viable Mtb bacilli to hydrolyze fluorescein diacetate to free fluorescein with detection of fluorescent mycobacteria by flow cytometric analysis, was recently developed.Methods: To evaluate this cytometric method, we tested 39 clinical isolates which were susceptible or resistant to isoniazid (INH) or rifampin (RIF), or ethambutol (EMB) by phenotypic or molecular DST methods and compared the results.Results: The susceptibility was determined by measuring the viability rate of Mtb and all the isolates which were tested with INH, RIF, and EMB showed susceptibility results concordant with those by the phenotypic solid and liquid media methods. The isolates having no mutations in the molecular DST but resistance in the conventional phenotypic DST were also resistant in this cytometric method. These results suggest that the flow cytometric DST method is faster than conventional agar phenotypic DST and may complement the results of molecular DST.Conclusion: In conclusion, the cytometric method could provide quick and more accurate information that would help clinicians to choose more effective drugs.

Olesya Danilevskaya(Laboratory of Clinical Pulmonology) ; Dmitry Sazonov(Department of Endoscopy) ; Tatyana Klypa(Intensive Care Unit) ; Fedor Zabozlaev(Department of Pathology) ; Elena Popova(Laboratory of Clinical Pulmonology) pp.273-275 https://doi.org/10.4046/trd.2022.0023
Yoo Jeong Rae(Department of Internal Medicine) ; Chang Lim Hyun(Jeju National University Hospital) ; Chang Suk Won(Jeju National University Hospital) ; Gil Myeong Seong(Jeju National University Hospital) pp.276-278 https://doi.org/10.4046/trd.2022.0030
Kazuto Matsunaga(Yamaguchi University) ; Stephen Milne(St. Paul’s Hospital, Vancouver, BC) ; Faisal Yunus(Universitas Indonesia-Persahabatan) ; ; Joon Young Choi(Incheon St. Mary’s Hospital) pp.279-282 https://doi.org/10.4046/trd.2022.0020

Tuberculosis & Respiratory Diseases