Displaying publications 121 - 140 of 148 in total

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  1. Kuan YC, How SH, Azian AA, Liam CK, Ng TH, Fauzi AR
    Ann Thorac Med, 2012 Apr;7(2):69-73.
    PMID: 22558010 DOI: 10.4103/1817-1737.94522
    Prolonged use of oral corticosteroids is a risk factor for osteoporosis. However, the effect of inhaled corticosteroids (ICS) on bone mineral density (BMD) of asthmatic patients remains controversial.
  2. Lu S, Shih JY, Jang TW, Liam CK, Yu Y
    Adv Ther, 2021 May;38(5):2038-2053.
    PMID: 33730350 DOI: 10.1007/s12325-021-01696-9
    Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are a standard of care in the first-line treatment of patients with EGFR mutation-positive metastatic non-small-cell lung cancer (NSCLC). EGFR mutations are relatively common in Asian patients with NSCLC, and there is an increasing number of studies supporting the effectiveness of the second-generation TKI afatinib in routine clinical practice in Asia. This article reviews these real-world studies investigating afatinib as first-line treatment for EGFR mutation-positive NSCLC in Asian patients. Evidence from real-world studies with afatinib in this patient population supports findings from randomized controlled trials (RCTs) showing that afatinib is associated with more favorable outcomes compared with the first-generation EGFR TKIs. The effectiveness of afatinib has also been shown in real-world studies in Asian patients with poor prognostic factors, who are often under-represented or excluded from RCTs, such as those with uncommon EGFR mutations, brain metastases, or poor performance status, and elderly patients. The tolerability profile of afatinib in the real-world setting reflects that seen in RCTs, with no new safety signals reported in real-world studies in Asian patients with EGFR mutation-positive NSCLC. Dose-modification strategies also seem to be effective in the real world, with results of the RealGido study, which included 44% Asian patients, confirming findings from prospective clinical trials showing that tolerability-guided afatinib dose modifications can reduce the incidence of adverse events without adversely affecting clinical outcomes. While further research, including clinical trial data, is needed, real-world data have also demonstrated the feasibility of sequential afatinib followed by the third-generation TKI osimertinib in T790M-positive EGFR mutation-positive patients, which showed longer overall survival. Together, these real-world results demonstrate the real-world clinical effectiveness of afatinib as first-line treatment for patients with EGFR mutation-positive NSCLC.
  3. Poh ME, Ampikaipakan S, Liam CK, Chai CS, Ramanaidoo D, Haja Mydin H
    J Asthma Allergy, 2021;14:629-640.
    PMID: 34140782 DOI: 10.2147/JAA.S309143
    BACKGROUND: There have been limited reports looking into the care of patients with asthma exacerbations admitted to tertiary hospitals in Southeast Asia. This study aims to determine the extent in which the 2019 Global Initiative for Asthma (GINA) guidelines were being met.

    METHODS: A retrospective study of patients with asthma exacerbations admitted to the University of Malaya Medical Centre (UMMC) and Pantai Hospital Kuala Lumpur (PHKL), Malaysia from 1 July 2019 to 31 December 2019.

    RESULTS: There were significant numbers of patients with previous admissions for asthma in both centres, with almost 50% experiencing an exacerbation in the previous year. Approximately 75% of the patients considered their asthma to be controlled when asked, despite many of them having had a history of acute exacerbations in the previous year. When cross-checked, the level of GINA-defined asthma control remained low, with only 6.4% of the patients deemed to have good control, while asthma was partially controlled in 25.6% of the patients and uncontrolled in 68% of the patients. About 72.1% of the patients reported daytime symptoms, 65.1% of the patients reported night-time symptoms, 70.9% of the patients required frequent usage of rescue inhalers and 72.1% of the patients reported some limitation in their activity prior to the current asthma exacerbation. Almost a quarter of the patients who were admitted had severe or life-threatening exacerbations as defined by GINA. These patients had more hospitalizations in a year and were more likely to have previous admissions requiring non-invasive and invasive ventilation. They were also more likely to be on GINA Step 5 treatment, had a lower mean percent predicted FEV1 and a higher baseline blood eosinophil count. Multivariate analysis revealed that baseline eosinophil count were independently associated with severe or life-threatening asthma exacerbations (odds ratio: 1.01, 95% confidence interval: 1.00-1.01, p=0.001). Failure to adhere to daily controller medications was high in this study (37.2%).

    CONCLUSION: Although the management of asthma exacerbations in tertiary hospitals in Southeast Asia is largely congruous with international guidelines, there is room for improvement. As there is a marked discrepancy between patient-perceived and guideline-defined asthma control, efforts to increase awareness on the dangers of uncontrolled asthma are warranted.

  4. Loong SK, Liam CK, Karunakaran R, Tan KK, Mahfodz NH, AbuBakar S
    J Int Med Res, 2024 Jan;52(1):3000605231214464.
    PMID: 38216150 DOI: 10.1177/03000605231214464
    An increasing number of reports have described the pathogenic nature of several non-classical Bordetella spp. Among them, Bordetella hinzii and Bordetella pseudohinzii have been implicated in a myriad of respiratory-associated infections in humans and animals. We report the isolation of a genetically close relative of B. hinzii and B. pseudohinzii from the sputum of a woman in her early 60s with extensive bronchiectasis who presented with fever and brown colored sputum. The isolate had initially been identified as Bordetella avium by API 20NE, the identification system for non-enteric Gram-negative rod bacteria. Sequencing of the 16S rDNA, ompA, nrdA, and genes used in the Bordetella multilocus sequence typing scheme could not resolve the identity of this Bordetella isolate. Whole-genome single nucleotide polymorphism analysis positioned the isolate between B. hinzii and B. pseudohinzii in the phylogenetic tree, forming a distinct cluster. Whole-genome sequencing enabled the further identification of this rare organism, and should be considered for wider applications, especially the confirmation of organism identity in the clinical diagnostic microbiology laboratory.
  5. Poh ME, Liam CK, Mun KS, Chai CS, Wong CK, Tan JL, et al.
    Thorac Cancer, 2019 09;10(9):1841-1845.
    PMID: 31350945 DOI: 10.1111/1759-7714.13156
    Adjuvant chemotherapy has long been indicated to extend survival in completely resected stage IB to IIIA non-small cell lung cancer (NSCLC). However, there is accumulating evidence that chemotherapy or chemoradiotherapy can induce epithelial-to-mesenchymal transition (EMT) in disseminated or circulating NSCLC cells. Here, we describe the first case of EMT as the cause of recurrence and metastasis in a patient with resected stage IIB lung adenosquamous carcinoma after adjuvant chemotherapy. We review the literature and explore the possible mechanisms by which EMT occurs in disseminated tumor cells (DTC) or circulating tumor cells (CTC) in response to adjuvant chemotherapy (cisplatin) as a stressor. We also explore the possible therapeutic strategies to reverse EMT in patients with recurrence. In summary, although adjuvant cisplatin-based chemotherapy in resected NSCLC does extend survival, it may lead to the adverse phenomenon of EMT in disseminated tumor cells (DTC) or circulating tumor cells (CTC) causing recurrence and metastasis.
  6. Tan SB, Liam CK, Pang YK, Leh-Ching Ng D, Wong TS, Wei-Shen Khoo K, et al.
    J Pain Symptom Manage, 2019 04;57(4):802-808.
    PMID: 30684635 DOI: 10.1016/j.jpainsymman.2019.01.009
    CONTEXT: Dyspnea is a common and distressing symptom in respiratory diseases. Despite advances in the treatment of various lung diseases, the treatment modalities for dyspnea remain limited.

    OBJECTIVES: This study aims to examine the effect of 20-minute mindful breathing on the rapid reduction of dyspnea at rest in patients with lung cancer, chronic obstructive pulmonary disease, and asthma.

    METHODS: We conducted a parallel-group, nonblinded, randomized controlled trial of standard care plus 20-minute mindful breathing vs. standard care alone for patients with moderate to severe dyspnea due to lung disease, named previously, at the respiratory unit of University Malaya Medical Centre in Malaysia, from August 1, 2017, to March 31, 2018.

    RESULTS: Sixty-three participants were randomly assigned to standard care plus a 20-minute mindful breathing session (n = 32) or standard care alone (n = 31), with no difference in their demographic and clinical characteristics. There was statistically significant reduction in dyspnea in the mindful breathing group compared with the control group at minute 5 (U = 233.5, n1 = 32, n2 = 31, mean rank1 = 23.28, mean rank2 = 37.72, z = -3.574, P 

  7. Yeoh SM, Kuo IC, Wang DY, Liam CK, Sam CK, De Bruyne JA, et al.
    Int Arch Allergy Immunol, 2003 Nov;132(3):215-20.
    PMID: 14646382 DOI: 10.1159/000074302
    BACKGROUND: The house dust mites Dermatophagoides pteronyssinus (Der p) and Blomia tropicalis (Blo t) are the most common house dust mite species in Southeast Asia. To date, there have only been a few studies on the sensitization profile of the general populations in Southeast Asia to house dust mites. The aim of this study was to determine the profiles of Der p and Blo t sensitization among Singaporean and Malaysian subjects.

    METHODS: Enzyme-linked immunosorbent assay was used to detect specific IgE to Der p and Blo t mite crude extracts as well as purified Der p 1, Der p 2 and Blo t 5 allergens. Sera used were from 229 Singaporean subjects (124 with rhinitis, 105 without rhinitis) and 143 Malaysian subjects (94 adults and 49 children with asthma).

    RESULTS: The sensitization profile of rhinitis subjects to the dust mite allergens used in this study was as follows: Blo t extract positive: 91/124 (73%); Blo t 5 positive: 62/124 (50%); Der p extract positive: 61/124 (49%); Der p 1 positive: 53/124 (43%); Der p 2 positive: 45/124 (36%). The nonrhinitis subjects' sensitization profile was as follows: Blo t extract positive: 60/105 (57%); Blo t 5 positive: 24/105 (23%); Der p extract positive: 38/105 (36%); Der p 1 positive: 14/105 (13%); Der p 2 positive: 17/105 (16%). The study of Malaysian asthmatic adults showed that 39% of them were sensitized to Der p 1, 32% to Der p 2 and 37% to Blo t 5. Among the asthmatic children, sensitization to Blo t 5, Der p 1 and Der p 2 was 90, 57 and 39%, respectively.

    CONCLUSION: This study clearly revealed that dual sensitization to B. tropicalis and D. pteronyssinus is common in the general populations of Singapore and Malaysia. Sensitization to Blo t 5 is more prevalent than to Der p 1 and Der p 2.
  8. Chai CS, Liam CK, Pang YK, Ng DL, Tan SB, Wong TS, et al.
    Int J Chron Obstruct Pulmon Dis, 2019 03 01;14:565-573.
    PMID: 30880946 DOI: 10.2147/COPD.S196109
    Introduction: The Spanish COPD guideline (GesEPOC) classifies COPD into four clinical phenotypes based on the exacerbation frequency and dominant clinical manifestations. In this study, we compared the disease-specific health-related quality of life (HRQoL) of patients with different clinical phenotypes.

    Methods: This was a cross-sectional study of patients with COPD attending the respiratory medicine clinic of University of Malaya Medical Centre from 1 June 2017 to 31 May 2018. Disease-specific HRQoL was assessed by using the COPD Assessment Test (CAT) and St George's Respiratory Questionnaire for COPD (SGRQ-c).

    Results: Of 189 patients, 28.6% were of non-exacerbator phenotype (NON-AE), 18.5% were of exacerbator with emphysema phenotype (AE NON-CB), 39.7% were of exacerbator with chronic bronchitis phenotype (AE CB), and 13.2% had asthma-COPD overlap syndrome phenotype (ACOS). The total CAT and SGRQ-c scores were significantly different between the clinical phenotypes (P<0.001). Patients who were AE CB had significantly higher total CAT score than those with ACOS (P=0.033), AE NON-CB (P=0.001), and NON-AE (P<0.001). Concerning SGRQ-c, patients who were AE CB also had a significantly higher total score than those with AE NON-CB (P=0.001) and NON-AE (P<0.001). However, the total SGRQ-c score of AE CB patients was only marginally higher than those who had ACOS (P=0.187). There was a significant difference in the score of each CAT item (except CAT 7) and SGRQ-c components between clinical phenotypes, with AE CB patients recording the highest score in each of them.

    Conclusion: Patients who were AE CB had significantly poorer HRQoL than other clinical phenotypes and recorded the worst score in each of the CAT items and SGRQ-c components. Therefore, AE CB patients may warrant a different treatment approach that focuses on the exacerbation and chronic bronchitis components.

  9. Chai CS, Liam CK, Poh ME, Ong DB, Pang YK, Cheah PL, et al.
    Cancer Manag Res, 2020;12:5439-5450.
    PMID: 32753961 DOI: 10.2147/CMAR.S253760
    BACKGROUND: This study aims to determine the predictors of acquired exon 20 T790M mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing epidermal growth factor receptor (EGFR) mutation following the failure of first- or second-generation EGFR-tyrosine kinase inhibitor (TKI).

    METHODS: This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017.

    RESULTS: A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84-6.25, p = 0.104).

    CONCLUSION: The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations.

  10. Chai CS, Ng DL, Bt Mos S, Ibrahim MAB, Tan SB, Pang YK, et al.
    BMC Pulm Med, 2023 Apr 28;23(1):150.
    PMID: 37118725 DOI: 10.1186/s12890-023-02436-1
    BACKGROUND: Management strategies of chronic obstructive pulmonary disease (COPD) need to be tailored to the forced expiratory volume in one second (FEV1), exacerbations, and patient-reported outcomes (PROs) of individual patients. In this study, we analyzed the association and correlation between the FEV1, exacerbations, and PROs of patients with stable COPD.

    METHODS: This was a post-hoc analysis of pooled data from two cross-sectional studies that were previously conducted in Malaysia from 2017 to 2019, the results of which had been published separately. The parameters measured included post-bronchodilator FEV1 (PB-FEV1), exacerbations, and scores of modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c). Descriptive, association, and correlation statistics were used.

    RESULTS: Three hundred seventy-four patients were included in the analysis. The PB-FEV1 predicted was

  11. Liam CK, Leow HR, How SH, Pang YK, Chua KT, Lim BK, et al.
    Asian Pac J Cancer Prev, 2014;15(1):321-6.
    PMID: 24528049
    BACKGROUND: Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non- small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients.

    MATERIALS AND METHODS: In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction.

    RESULTS: EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94- 18.17; p=0.002).

    CONCLUSIONS: In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.

  12. Price D, David-Wang A, Cho SH, Ho JC, Jeong JW, Liam CK, et al.
    J Asthma Allergy, 2015;8:93-103.
    PMID: 26445555 DOI: 10.2147/JAA.S82633
    PURPOSE: Asthma is a global health problem, and asthma prevalence in Asia is increasing. The REcognise Asthma and LInk to Symptoms and Experience Asia study assessed patients' perception of asthma control and attitudes toward treatment in an accessible, real-life adult Asian population.
    PATIENTS AND METHODS: An online survey of 2,467 patients with asthma from eight Asian countries/regions, aged 18-50 years, showed greater than or equal to two prescriptions in previous 2 years and access to social media. Patients were asked about their asthma symptoms, exacerbations and treatment type, views and perceptions of asthma control, attitudes toward asthma management, and sources of asthma information.
    RESULTS: Patients had a mean age of 34.2 (±7.4) years and were diagnosed with asthma for 12.5 (±9.7) years. Half had the Global Initiative for Asthma-defined uncontrolled asthma. During the previous year, 38% of patients visited the emergency department, 33% were hospitalized, and 73% had greater than or equal to one course of oral corticosteroids. About 90% of patients felt that their asthma was under control, 82% considered their condition as not serious, and 59% were concerned about their condition. In all, 66% of patients viewed asthma control as managing attacks and 24% saw it as an absence of or minimal symptoms. About 14% of patients who correctly identified their controller inhalers had controlled asthma compared to 6% who could not.
    CONCLUSION: Patients consistently overestimated their level of asthma control contrary to what their symptoms suggest. They perceived control as management of exacerbations, reflective of a crisis-oriented mind-set. Interventions can leverage on patients' trust in health care providers and desire for self-management via a new language to generate a paradigm shift toward symptom control and preventive care.
    KEYWORDS: asthma control; attitudes; perception
  13. Price D, David-Wang A, Cho SH, Ho JC, Jeong JW, Liam CK, et al.
    J Asthma, 2016 09;53(7):761-9.
    PMID: 27096388 DOI: 10.3109/02770903.2016.1141951
    OBJECTIVE: We examined the physician perspectives on asthma management in Asia.

    METHODS: An online/face-to-face, questionnaire-based survey of respiratory specialists and primary care physicians from eight Asian countries/region was carried out. The survey explored asthma control, inhaler selection, technique and use; physician-patient communications and asthma education. Inclusion criteria were >50% of practice time spent on direct patient care; and treated >30 patients with asthma per month, of which >60% were aged >12 years.

    RESULTS: REALISE Asia (Phase 2) involved 375 physicians with average 15.9(±6.8) years of clinical experience. 89.1% of physicians reporting use of guidelines estimated that 53.2% of their patients have well-controlled (GINA-defined) asthma. Top consideration for inhaler choice was asthma severity (82.4%) and lowest, socio-economic status (32.5%). Then 54.7% of physicians checked their patients' inhaler techniques during consultations but 28.2(±19.1)% of patients were using their inhalers incorrectly; 21.1-57.9% of physicians could spot improper inhaler techniques in video demonstrations. And 79.6% of physicians believed combination inhalers could increase adherence because of convenience (53.7%), efficacy (52.7%) and usability (18.9%). Initial and follow-up consultations took 16.8(±8.4) and 9.2(±5.3) minutes, respectively. Most (85.1%) physicians used verbal conversations and least (24.5%), video demonstrations of inhaler use; 56.8% agreed that patient attitudes influenced their treatment approach.

    CONCLUSION: Physicians and patients have different views of 'well-controlled' asthma. Although physicians informed patients about asthma and inhaler usage, they overestimated actual usage and patients' knowledge was sub-optimal. Physician-patient interactions can be augmented with understanding of patient attitudes, visual aids and ancillary support to perform physical demonstrations to improve treatment outcomes.

  14. Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al.
    Ann Oncol, 2015 Sep;26(9):1883-1889.
    PMID: 26105600 DOI: 10.1093/annonc/mdv270
    BACKGROUND: The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

    PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.

    RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.

    CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

  15. Rajadurai P, Cheah PL, How SH, Liam CK, Annuar MAA, Omar N, et al.
    Lung Cancer, 2019 10;136:65-73.
    PMID: 31446227 DOI: 10.1016/j.lungcan.2019.08.005
    In the recent years, increased understanding of the molecular profiles of non-small cell lung cancer (NSCLC) has allowed for targeted treatment of actionable genetic mutations. The management of NSCLC now requires multiple molecular tests to guide the treatment strategy. In the light of this, there is a need to establish a molecular testing consensus statement for advanced NSCLC patients in Malaysia. This Malaysian consensus statement was developed by a panel of experts, chaired by a pathologist and composed of three other pathologists, four respiratory physicians and three oncologists. It reflects currently available scientific data and adaptations of recommendations from international guidelines to the local landscape. Expert recommendations on different aspects of molecular testing agreed upon by the panel are provided as structured discussions. These recommendations address the appropriate patients and samples to be tested, as well as when and how these tests should be performed. The algorithms for molecular testing in metastatic NSCLC, in the first line setting and upon disease progression beyond first line therapy, were developed.
  16. Chai CS, Mos SB, Ng DL, Goh GM, Su AT, Ibrahim MAB, et al.
    BMC Pulm Med, 2020 Sep 29;20(1):254.
    PMID: 32993591 DOI: 10.1186/s12890-020-01295-4
    BACKGROUND: The Spanish chronic obstructive pulmonary disease (COPD) guideline phenotypes patients according to the exacerbation frequency and COPD subtypes. In this study, we compared the patients' health-related quality of life (HRQoL) according to their COPD phenotypes.

    METHODS: This was a cross-sectional study of COPD patients who attended the outpatient clinic of the Serian Divisional Hospital and Bau District Hospital from 23th January 2018 to 22th January 2019. The HRQoL was assessed using modified Medical Research Council (mMRC), COPD Assessment Test (CAT), and St George's Respiratory Questionnaire for COPD (SGRQ-c).

    RESULTS: Of 185 patients, 108 (58.4%) were non-exacerbators (NON-AE), 51 (27.6%) were frequent exacerbators (AE), and the remaining 26 (14.1%) had asthma-COPD overlap (ACO). Of AE patients, 42 (82.4%) had chronic bronchitis and only 9 (17.6%) had emphysema. Of the 185 COPD patients, 65.9% had exposure to biomass fuel and 69.1% were ex- or current smokers. The scores of mMRC, CAT, and SGRQ-c were significantly different between COPD phenotypes (p 

  17. Ninomiya K, Arimura H, Chan WY, Tanaka K, Mizuno S, Muhammad Gowdh NF, et al.
    PLoS One, 2021;16(1):e0244354.
    PMID: 33428651 DOI: 10.1371/journal.pone.0244354
    OBJECTIVES: To propose a novel robust radiogenomics approach to the identification of epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC) using Betti numbers (BNs).

    MATERIALS AND METHODS: Contrast enhanced computed tomography (CT) images of 194 multi-racial NSCLC patients (79 EGFR mutants and 115 wildtypes) were collected from three different countries using 5 manufacturers' scanners with a variety of scanning parameters. Ninety-nine cases obtained from the University of Malaya Medical Centre (UMMC) in Malaysia were used for training and validation procedures. Forty-one cases collected from the Kyushu University Hospital (KUH) in Japan and fifty-four cases obtained from The Cancer Imaging Archive (TCIA) in America were used for a test procedure. Radiomic features were obtained from BN maps, which represent topologically invariant heterogeneous characteristics of lung cancer on CT images, by applying histogram- and texture-based feature computations. A BN-based signature was determined using support vector machine (SVM) models with the best combination of features that maximized a robustness index (RI) which defined a higher total area under receiver operating characteristics curves (AUCs) and lower difference of AUCs between the training and the validation. The SVM model was built using the signature and optimized in a five-fold cross validation. The BN-based model was compared to conventional original image (OI)- and wavelet-decomposition (WD)-based models with respect to the RI between the validation and the test.

    RESULTS: The BN-based model showed a higher RI of 1.51 compared with the models based on the OI (RI: 1.33) and the WD (RI: 1.29).

    CONCLUSION: The proposed model showed higher robustness than the conventional models in the identification of EGFR mutations among NSCLC patients. The results suggested the robustness of the BN-based approach against variations in image scanner/scanning parameters.

  18. Eich A, Urban V, Jutel M, Vlcek J, Shim JJ, Trofimov VI, et al.
    COPD, 2017 Oct;14(5):476-483.
    PMID: 28753067 DOI: 10.1080/15412555.2017.1335697
    Interleukin (IL)-17A may be an underlying factor in the pathophysiology of chronic obstructive pulmonary disease (COPD). Anti-IL-17 monoclonal antibodies have been used successfully in treating several immune-mediated inflammatory diseases. This phase 2, randomized, placebo-controlled, double-blind, parallel-group, proof-of-concept study is the first clinical study evaluating the efficacy and safety of the anti-IL-17A monoclonal antibody CNTO 6785 in patients with symptomatic moderate-to-severe COPD. Patients were treated with CNTO 6785 (n = 93) or placebo (n = 94) intravenously at Weeks 0, 2, and 4 (induction), then Weeks 8 and 12, and followed till Week 24. The primary efficacy endpoint was the change from baseline in pre-bronchodilator percent-predicted forced expiratory volume in 1 second at Week 16. Samples were collected at all visits for pharmacokinetic (PK) evaluation, and standard safety assessments were performed. The mean difference in the primary efficacy endpoint between CNTO 6785 and placebo was not statistically significant (-0.49%; p = 0.599). No other efficacy endpoints demonstrated clinically or statistically significant differences with CNTO 6785 compared with placebo. CNTO 6785 was generally well tolerated; no major safety signals were detected. The most frequently reported treatment-emergent adverse events were infections and infestations; however, no notable differences were observed between CNTO 6785 and placebo in terms of rates of infections. PK results suggested that the steady state of serum CNTO 6785 concentration was reached within 16 weeks. These results suggest that IL-17A is unlikely to be a dominant driver in the pathology of, or a viable therapeutic target for, COPD. ClinicalTrials.gov Identifier: NCT01966549; EudraCT Identifier: 2012-003607-36.
  19. Soo CI, Ong DB, Chin KK, Sia LC, Munusamy V, Ibrahim NH, et al.
    Respirol Case Rep, 2023 Jul;11(7):e01181.
    PMID: 37350988 DOI: 10.1002/rcr2.1181
    Neoadjuvant chemotherapy is a therapeutic option for potentially resectable non-small cell lung cancer (NSCLC). The role of neoadjuvant targeted therapy (NTT) remains less explored. This case highlights the use of neoadjuvant osimertinib in a case of advanced NSCLC. A 67-year-old woman had a left lower lobe lung mass measuring 5.0 × 5.1 × 7.0 cm with an enlarged subcarinal lymph node (LN) on her positron emission tomography scan. Following biopsy, a diagnosis of stage IIIB N2 (cT3N2M0) EGFR exon 19 deletion mutation-positive lung adenocarcinoma was established. NTT using osimertinib 80 mg once daily was commenced. Subsequent re-imaging at 3 months (ycT2bN2M0), 6 months (ycT1cN2M0) and 9 months showed tumour downstaging and resolution of the subcarinal LN (ycT1cN0M0). She underwent left lower lobectomy with systematic nodal dissection. All surgical specimens demonstrated no evidence of malignant cells (ypT0N0). Osimertinib could be the preferred NTT for potentially resectable NSCLC.
  20. Ninomiya K, Arimura H, Tanaka K, Chan WY, Kabata Y, Mizuno S, et al.
    Comput Methods Programs Biomed, 2023 Jun;236:107544.
    PMID: 37148668 DOI: 10.1016/j.cmpb.2023.107544
    OBJECTIVES: To elucidate a novel radiogenomics approach using three-dimensional (3D) topologically invariant Betti numbers (BNs) for topological characterization of epidermal growth factor receptor (EGFR) Del19 and L858R mutation subtypes.

    METHODS: In total, 154 patients (wild-type EGFR, 72 patients; Del19 mutation, 45 patients; and L858R mutation, 37 patients) were retrospectively enrolled and randomly divided into 92 training and 62 test cases. Two support vector machine (SVM) models to distinguish between wild-type and mutant EGFR (mutation [M] classification) as well as between the Del19 and L858R subtypes (subtype [S] classification) were trained using 3DBN features. These features were computed from 3DBN maps by using histogram and texture analyses. The 3DBN maps were generated using computed tomography (CT) images based on the Čech complex constructed on sets of points in the images. These points were defined by coordinates of voxels with CT values higher than several threshold values. The M classification model was built using image features and demographic parameters of sex and smoking status. The SVM models were evaluated by determining their classification accuracies. The feasibility of the 3DBN model was compared with those of conventional radiomic models based on pseudo-3D BN (p3DBN), two-dimensional BN (2DBN), and CT and wavelet-decomposition (WD) images. The validation of the model was repeated with 100 times random sampling.

    RESULTS: The mean test accuracies for M classification with 3DBN, p3DBN, 2DBN, CT, and WD images were 0.810, 0.733, 0.838, 0.782, and 0.799, respectively. The mean test accuracies for S classification with 3DBN, p3DBN, 2DBN, CT, and WD images were 0.773, 0.694, 0.657, 0.581, and 0.696, respectively.

    CONCLUSION: 3DBN features, which showed a radiogenomic association with the characteristics of the EGFR Del19/L858R mutation subtypes, yielded higher accuracy for subtype classifications in comparison with conventional features.

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