Increased exacerbations of bronchiectasis following recovery from mild COVID-19 in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND AND OBJECTIVE: Respiratory viral infection is a common trigger of bronchiectasis exacerbation. Knowledge of the intermediate to long-term effect of COVID-19 on bronchiectasis is poor. METHODS: A retrospective cohort study of patient records was conducted to assess the frequency of bronchiectasis exacerbation following recovery from mild-to-moderate COVID-19. The exacerbation frequency at baseline, using 2019 and 2019-2021 data, was compared with that during the 1 year following recovery. RESULTS: A total of 234 adult patient records who had a confirmed diagnosis of bronchiectasis were identified, of whom 52 (22.2%) were classified as the COVID-19 group. Patients with COVID-19 had significantly more frequent annual exacerbations of bronchiectasis (total exacerbations and hospitalizations). Compared with 2019-2021 data, the total exacerbation frequency decreased by 0.1 ± 0.51 per year among non-COVID-19 patients but increased by 0.68 ± 1.09 per year among the COVID-19 group (p < 0.001). Compared with 2019 only data, exacerbation frequency decreased by 0.14 ± 0.79 per year among non-COVID-19 patients but increased by 0.76 ± 1.17 per year in the COVID-19 group, p < 0.001. The annual frequency of hospitalization for bronchiectasis increased by 0.01 ± 0.32 per year among non-COVID-19 patients and increased by 0.39 ± 1.06 per year in the COVID-19 group (p < 0.001) compared with 2019 to 2021 data. When compared with only 2019 data, it remained unchanged at 0 ± 0.43 per year among non-COVID-19 patients but increased to 0.38 ± 1.12 per year among COVID-19 patients (p < 0.001). CONCLUSION: Mild-to-moderate COVID-19 was associated with an increase in frequency of bronchiectasis exacerbation and frequency of hospitalizations following recovery.

Worsening of asthma control after recovery from mild to moderate COVID-19 in patients from Hong Kong.

BACKGROUND: While there are postulations that asthma is potentially associated with severe coronavirus disease 2019 (COVID-19), there has been conflicting results from studies on the impact mild-to-moderate COVID-19 on asthma control after recovery. METHODS: A case control study on the association between mild-to-moderate COVID-19 and asthma control post infection was conducted. The primary outcome was a reduction in Asthma Control Test (ACT) score by ≥ 3 points post-COVID infection. The secondary outcomes included the change in ACT score, the proportion of patient with ACT score who dropped to ≤ 15 on enrolment visit and the need for escalation of asthma maintenance therapy. RESULTS: Out of the total of 221 adult patients with asthma recruited, 111 had mild-to-moderate COVID-19 within 30 to 270 days prior to study enrolment. The adjusted odds ratio (aOR) for a reduction in ACT score by ≥ 3 points after COVID-19 was 3.105 (95% CI = 1.385-6.959, p = 0.006). The odds of escalation of asthma maintenance therapy by at least 1 Global Initiative for Asthma (GINA) step was 4.733 (95% CI = 1.151-19.467, p = 0.031) and asthma patient are more likely to become uncontrolled after COVID-19 [aOR = 5.509 (95% CI = 1.061-28.600, p = 0.042)]. CONCLUSION: Mild-to-moderate COVID-19 among asthma patients, upon recovery, was associated with worsening of asthma symptom, lower ACT score, a higher need for escalation of asthma maintenance therapy and more uncontrolled asthma.

Validation of diagnostic coding for bronchiectasis in an electronic health record system in Hong Kong.

BACKGROUND AND OBJECTIVE: Electronic medical record (EMR) databases can facilitate epidemiology research in various diseases including bronchiectasis. Given the diagnostic challenges of bronchiectasis, the validity of the coding in EMR requires clarification. We aimed to assess the validity of International Classification of Diseases, 9th Revision (ICD-9) code algorithms for identifying bronchiectasis in the territory-wide electronic medical health record system of Clinical Data Analysis and Reporting System (CDARS) in Hong Kong. MATERIALS AND METHODS: Adult patients who had the diagnosis of bronchiectasis input from Queen Mary Hospital in 2011-2020 were identified using the ICD-9 code of 494 by CDARS. All patients who had high resolution computed tomography (HRCT) were reviewed by respiratory specialists to confirm the presence of bronchiectasis on HRCT. RESULTS: A total of 19 617 patients who had the diagnostic code of bronchiectasis among all public hospitals in Hong Kong and 1866 in Queen Mary Hospital in the same period. Six hundred and forty-eight cases were randomly selected and validated using medical record and HRCT review by a respiratory specialist. The overall positive predictive value (PPV) was 92.7% (95% CI 90.7-94.7). CONCLUSIONS: This was the first ICD-9 coding validation for bronchiectasis in Hong Kong CDARS. Our study demonstrated that using ICD-9 code of 494 was reliable to support utility of CDARS database for further clinical research on bronchiectasis.

Prediction model on disease recurrence for low risk resected stage I lung adenocarcinoma.

BACKGROUND AND OBJECTIVE: Although stage I non-small cell lung carcinoma (NSCLC) typically carries a good prognosis following complete resection, early disease recurrence can occur. An accurate survival prediction model would help refine a follow-up strategy and personalize future adjuvant therapy. We developed a post-operative prediction model based on readily available clinical information for patients with stage I adenocarcinoma. METHODS: We retrospectively studied the disease-free survival (DFS) of 408 patients with pathologically confirmed low-risk stage I adenocarcinoma of lung who underwent curative resection from 2013 to 2017. A tree-based method was employed to partition the cohort into subgroups with distinct DFS outcome and stepwise risk ratio. These covariates were included in multivariate analysis to build a scoring system to predict disease recurrence. The model was subsequently validated using a 2011-2012 cohort. RESULTS: Non-smoker status, stage IA disease, epidermal-growth factor receptor mutants and female gender were associated with better DFS. Multivariate analysis identified smoking status, disease stage and gender as factors necessary for the scoring system and yielded 3 distinct risk groups for DFS [99.4 (95% CI 78.3-125.3), 62.9 (95% CI 48.2-82.0), 33.7 (95% CI 24.6-46.1) months, p < 0.005]. External validation yielded an area under the curve by receiver operating characteristic analysis of 0.863 (95% CI 0.755-0.972). CONCLUSION: The model could categorize post-operative patients using readily available clinical information, and may help personalize a follow-up strategy and future adjuvant therapy.

Association of genetic polymorphisms of CYP3A4 and CYP2D6 with gefitinib-induced toxicities.

Dermatological, gastrointestinal and hepatic toxicities are the most common adverse events associated with gefitinib use. Gefitinib is metabolized by cytochrome P450. Inconsistent associations of single nucleotide genetic polymorphisms of CYP450 and gefitinib-induced adverse effects were reported. We aim to investigate the association between CYP450 genetic polymorphism and the development of gefitinib-associated adverse events. A retrospective cohort study of Chinese patients with metastatic nonsmall cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations who received first-line gefitinib treatment was conducted. Single nucleotide polymorphisms (SNPs) of CYP2D6, CYP3A4 and CYP3A5 were assayed using a multiplex SNP microarray. Risks of development of gefitinib-induced toxicities associated with different SNPs were determined. Among the 152 patients treated with gefitinib, 52 (34.2%) had gefitinib-induced hepatotoxicity, 113 (74.3%) had cutaneous reactions and 53 (34.9%) had gastrointestinal adverse effects. CYP2D6*41 CT, CYP2D6*10 AA and CYP3A4*1/*1G TT genotypes were significantly associated with hepatic, cutaneous and gastrointestinal adverse effects [odds ratio (OR) 3.773; (95% confidence interval {CI},1.046-13.610; P = 0.043), 3.368 (95% CI, 1.000-11.345; P = 0.050) and 20.000 (95% CI, 2.381-167.965; P = 0.006), respectively]. CYP2D6*41 CT, CYP2D6*10 AA and CYP3A4*1/*1G TT genotypes may be associated with increased risks of gefitinib-induced toxicities in the liver, skin and gastrointestinal tract.

Risk factors for Pseudomonas aeruginosa colonization in non-cystic fibrosis bronchiectasis and clinical implications.

BACKGROUND: Pseudomonas aeruginosa is one of the commonest bacteria colonizing the airway in patients with non-cystic fibrosis bronchiectasis. Pseudomonas aeruginosa colonization is associated with poor outcomes in patients with bronchiectasis, including rapid decline in lung function, exacerbation frequency and hospitalization. METHODS: A cross-sectional study in Queen Mary Hospital, Hong Kong that included 350 Chinese patients with non-cystic fibrosis bronchiectasis to investigate the risk factors for Pseudomonas aeruginosa colonization and clinical implications on disease outcomes. DISCUSSIONS: Pseudomonas aeruginosa colonization was more commonly found in patients with longer duration of bronchiectasis and those on proton pump inhibitors (PPIs) with adjusted ORs of 1.066 (95% CI = 1.036-1.096, p < 0.001) and 2.815 (95% CI = 1.307-6.064, p = 0.008) respectively. Patients with Pseudomonas aeruginosa colonization have more extensive lung involvement and higher risks of exacerbation requiring hospitalization with adjusted ORs of 2.445 (95% CI = 1.283-4.657, p = 0.007) and 2.745 (95% CI = 1.012-7.449, p = 0.047) respectively. Pseudomonas aeruginosa colonization is more common among patients with longer duration of bronchiectasis and those on PPI. Pseudomonas aeruginosa colonization is associated with more extensive lung involvement and higher risks of exacerbation requiring hospitalization.

Modelling the impact of travel restrictions on COVID-19 cases in Hong Kong in early 2020.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) led to pandemic that affected almost all countries in the world. Many countries have implemented border restriction as a public health measure to limit local outbreak. However, there is inadequate scientific data to support such a practice, especially in the presence of an established local transmission of the disease. OBJECTIVE: To apply a metapopulation Susceptible-Exposed-Infectious-Recovered (SEIR) model with inspected migration to investigate the effect of border restriction as a public health measure to limit outbreak of coronavirus disease 2019. METHODS: We apply a modified metapopulation SEIR model with inspected migration with simulating population migration, and incorporating parameters such as efficiency of custom inspection in blocking infected travelers in the model. The population sizes were retrieved from government reports, while the number of COVID-19 patients were retrieved from Hong Kong Department of Health and China Centre for Disease Control (CDC) data. The R0 was obtained from previous clinical studies. RESULTS: Complete border closure can help to reduce the cumulative COVID-19 case number and mortality in Hong Kong by 13.99% and 13.98% respectively. To prevent full occupancy of isolation facilities in Hong Kong; effective public health measures to reduce local R0 to below 1.6 was necessary, apart from having complete border closure. CONCLUSIONS: Early complete travel restriction is effective in reducing cumulative cases and mortality. However, additional anti-COVID-19 measures to reduce local R0 to below 1.6 are necessary to prevent COVID-19 cases from overwhelming hospital isolation facilities.

Role of early definitive management for newly diagnosed malignant pleural effusion related to lung cancer.

BACKGROUND AND OBJECTIVE: The advent of effective anti-cancer therapy has brought about uncertainty on the benefit of early definitive measures for newly diagnosed MPE from lung cancer. This study aims to investigate the outcomes of MPE in this setting. METHODS: Lung cancer patients with MPE at first presentation to a tertiary care hospital were followed up till death or censored from 2011 to 2018. Early MPE control measures included chemical pleurodesis or IPC before or shortly after oncological treatment. Predictors of time to MPE re-intervention were identified with Cox proportional hazard analyses. RESULTS: Of the 509 records screened, 233 subjects were eligible. One hundred and twenty-seven subjects received oral targeted therapy as first-line treatment and 34 (26.8%) underwent early definitive MPE control measures. Early MPE control measures in addition to targeted therapy, as compared to targeted therapy alone, significantly reduced the subsequent need of MPE re-intervention (23.5% vs 53.8%, P = 0.002). Similar benefits from MPE control measures were found in groups receiving systemic anti-cancer therapy or best supportive care (0% vs 52%, P = 0.003; 18% vs 56.7%, P = 0.024, respectively). In the group with targetable mutations, both early MPE control measures (HR: 0.25, 95% CI: 0.12-0.53, P < 0.001) and the use of targeted therapy (HR: 0.22, 95% CI: 0.10-0.46, P < 0.001) were independently associated with longer time to MPE re-interventions. CONCLUSION: Early MPE control measures in lung cancer has additional benefits on reducing the need and prolonging the time to MPE re-intervention, independent of anti-cancer therapies.

Efficacy of gefitinib at reduced dose in EGFR mutant non-small cell lung carcinoma.

As a first-generation epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib was approved by the US Food and Drug Administration for treatment of advanced non-small cell carcinoma with sensitizing EGFR mutations. Gefitinib is known to have adverse effects, which may necessitate dose reduction or even change to alternative preparation of epidermal growth factor receptor-tyrosine kinase inhibitor. There has been concern on dose reduction resulting in reduced dose gefitinib, especially on its efficacy. This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong that included 159 Chinese patients with advanced adenocarcinoma of lung that carried sensitizing EGFR mutations and had received gefitinib as first-line treatment. Patients who had reduced dose at 250 mg alternate day were compared with those who were able to maintain on standard dose of gefitinib at 250 mg daily. The primary end-point was progression-free survival. Among the 159 patients, 17 (10.7 %) of them were on reduced dose gefitinib, 14 among the 17 patients (82.4%) because of hepatotoxicity, and 3 (17.6%) because of cutaneous side effects. Patients on reduced dose and standard dose of gefitinib have comparable median progression-free survival. Hazard ratio was 1.121 (95% confidence interval = 0. 655-1.917, P-value = 0.678) for the reduced dose group and 3.385 for the standard dose group (95% confidence interval = 2.181-5.255) respectively (P-value < 0.001). Dose reduction in gefitinib to 250 mg alternate day in response to adverse effects was not associated with inferior outcome for patients on first-line gefitinib for advanced non-small cell carcinoma. Dose reduction is a feasible option for patients who have significant adverse effects with gefitinib.

CPAP therapy for patients with sleep apnea and type 2 diabetes mellitus improves control of blood pressure.

PURPOSE: Obstructive sleep apnea (OSA) is highly associated with type 2 diabetes mellitus (DM), and treatment of OSA may have a positive impact on cardiometabolic profile. This study investigates the effects of continuous positive airway pressure (CPAP) treatment on glycemic control and cardiometabolic parameters in patients with diabetes. METHODS: Diabetic patients, who were newly diagnosed of OSA with an apnea hypopnea index (AHI) ≥15 and HbA1c ≥7%, were randomly assigned to either CPAP treatment or no treatment (control) for 3 months. Measurements included HbA1c, blood pressure, fasting glucose and lipids, urinary albumin, and peripheral arterial tonometry (to assess endothelial function). RESULTS: Sixty-four patients (52 men) were randomized, with mean (±SD) age of 55.0 ± 9.6 years, body mass index of 29.9 ± 5.3 kg/m2, HbA1c of 8.1 ± 1.1%, and AHI of 45.3 ± 23.2 events/h. In the intention-to-treat analysis, no significant change in HbA1c but reduction of systolic (10 mmHg (-18 to -2), p < 0.05) and diastolic (6 mmHg (-11 to -1), p < 0.05) blood pressures were found in the CPAP group compared to the control group. Excluding those with medication changes or initiated dietary program during the study period and those who dropped out, CPAP treatment decreased HbA1c (intervention group, n = 27; control group, n = 26) by 0.4% (-0.7 to -0.1), p = 0.027. CONCLUSIONS: In patients with type 2 DM and moderate to severe OSA, 3 months of CPAP therapy did not decrease HbA1c but lowered systolic and diastolic blood pressures. In view of a potentially limited effect size of CPAP treatment on glycemic control, sample size estimation for future randomized controlled studies must make adequate allowance for influence from external factors of medications/diet and CPAP use.

Outcomes among patients with chronic obstructive pulmonary disease after recovery from COVID-19 infection of different severity.

While studies have suggested increased risks of severe COVID-19 infection in chronic obstructive pulmonary disease (COPD), the persistent and delayed consequences of COVID-19 infection on patients with COPD upon recovery remain unknown. A prospective clinical study was conducted in Hong Kong to investigate the persistent and delayed outcomes of patients with COPD who had COVID-19 infection of different severity (mild-moderate COVID-19 and severe COVID-19), compared with those who did not. Chinese patients with COPD ≥ 40 years old were recruited from March to September 2021. They were prospectively followed up for 24.9 ± 5.0 months until 31st August 2023. The primary outcome was the deterioration in COPD control defined as the change in mMRC dyspnea scale. The secondary outcomes included the change in exacerbation frequency and non-COVID-19 respiratory mortality (including death from COPD exacerbation or bacterial pneumonia). 328 patients were included in the analysis. Patients with mild-moderate and severe COVID-19 infection had statistically significant increased risks of worsening of mMRC dyspnoea scale by increase in 1 score from baseline to follow-up with adjusted odds ratios of 4.44 (95% CI = 1.95-10.15, p < 0.001) and 6.77 (95% CI = 2.08-22.00, p = 0.001) respectively. Patients with severe COVID-19 infection had significantly increased risks of increase in severe COPD exacerbation frequency with adjusted odds ratios of 4.73 (95% CI = 1.55-14.41, p = 0.006) non-COVID-19 respiratory mortality from COPD exacerbation or pneumonia with adjusted hazard ratio of 11.25 (95% CI = 2.98-42.45, p < 0.001). After recovery from COVID-19, worsening of COPD control from worsening of dyspnea, increase in severe exacerbation frequency to non-COVID-19 respiratory mortality (COPD exacerbation and pneumonia) was observed among patients with severe COVID-19. Mild to moderate COVID-19 was also associated with symptomatic deterioration.

Real-World Effectiveness Study of Nirmatrelvir-Ritonavir or Molnupiravir in Hospitalized Unvaccinated Patients with Chronic Respiratory Diseases and Moderate COVID-19 at Presentation.

Introduction: Nirmatrelvir-ritonavir (NMV-r) and molnupiravir (MOL) were developed as out-patient anti-viral for mild COVID-19. There was limited data on their role in treating COVID-19 for hospitalized patients, especially among adult patients who are unvaccinated and had chronic respiratory diseases. Methods: A territory-wide retrospective study was conducted in Hong Kong to compare the efficacy of NMV-r and MOL against COVID-19 in unvaccinated adult patients with asthma, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung diseases presenting with moderate COVID-19 from 16th February 2022 to 15th March 2023. Results: A total of 1354 patients were included, 738 received NMV-r and 616 received MOL. NMV-r was more effective in reducing 90-day mortality with adjusted hazard ratios (aHR) of 0.508 (95% confidence interval [CI] = 0.314-0.822, p = 0.006). Patients who received NMV-r also had significantly shorter length of stay (LOS) than those receiving MOL, with median LOS of 4 (Interquartile range [IQR] = 2-7) for NMV-r and 6 (IQR = 3-10) for MOL (p-value < 0.001). There was no statistically significant difference in the development of respiratory failure and severe respiratory failure in the two groups. Discussion: NMV-r was more effective than MOL among unvaccinated adults with chronic respiratory diseases who were hospitalized for moderate COVID-19 without hypoxaemia on admission.

Systemic immune-inflammation index in predicting hospitalized bronchiectasis exacerbation risks and disease severity.

Background: Bronchiectasis is a common respiratory disease with neutrophilic inflammation being the predominant pathophysiology. Systemic immune-inflammation index (SII) is a simple and readily available biomarker being studied in various conditions including asthma, chronic obstructive pulmonary disease, and interstitial lung disease, but not in bronchiectasis. We aim to investigate the prognostic role of SII in bronchiectasis with this study. Methods: A retrospective cohort study in Chinese patients with non-cystic fibrosis (CF) bronchiectasis was conducted in Hong Kong, to investigate the association between baseline SII and of hospitalized bronchiectasis exacerbation risk over 4.5 years of follow-up, as well as correlating with disease severity in bronchiectasis. The baseline SII in 2018 was calculated based on stable-state complete blood count. Results: Among 473 Chinese patients with non-CF bronchiectasis were recruited, 94 of the patients had hospitalized bronchiectasis exacerbation during the follow-up period. Higher SII was associated with increased hospitalized bronchiectasis exacerbation risks with adjusted odds ratio (aOR) of 1.001 [95% confidence interval (CI): 1.000-1.001, P=0.003] for 1 unit (cells/µL) increase in SII count and aOR of 1.403 (95% CI: 1.126-1.748, P=0.003) for 1 standard deviation (SD) increase in SII. SII was found to have significant negative association with baseline forced expiratory volume in the first second (FEV1) (in litre and percentage predicted), forced vital capacity (FVC) in percentage; and significant positive correlation with the extent of bronchiectasis and baseline neutrophil to lymphocyte ratio (NLR). Conclusions: SII could serve as biomarker to predict the risks of hospitalized exacerbation in bronchiectasis patients, as well as correlating with the disease severity.

Baseline neutrophil-to-lymphocyte ratio as a predictor of response to hospitalized bronchiectasis exacerbation risks.

Background: Bronchiectasis is a disease with predominantly neutrophilic inflammation. As a readily available biomarker, there is little evidence to support the use of blood neutrophil-to-lymphocyte ratio (NLR) to predict bronchiectasis exacerbation severe enough to warrant hospitalization. Methods: A registry-based retrospective cohort study was conducted at a in Hong Kong. Chinese patients with non-cystic fibrosis (CF) bronchiectasis were retrospectively reviewed and subsequently followed up to investigate the association of NLR and the need for hospitalization for bronchiectasis exacerbation. Data on the NLR for patients in a clinically stable state in 2018 were collected and patients followed up from 1 January 2019 to 31 December 2022. The primary outcome was the need for hospitalization due to bronchiectasis exacerbation over the next 4 years. Results: We reviewed 473 Chinese patients with non-CF bronchiectasis, of whom 94 required hospitalization for bronchiectasis exacerbation during the 4-year follow-up period. Multi-variable logistic regression adjusted for E-FACED score (Exacerbation, Forced expiratory volume in 1 s (FEV1), Age, Chronic colonization, Extension, and Dyspnea score), gender, age, smoking status, and presence of co-existing chronic obstructive pulmonary disease (COPD) was conducted to compare patients with highest and lowest quartile NLR. Results revealed that those with NLR at the highest quartile were at increased risk of hospitalization for bronchiectasis exacerbation with an adjusted odds ratio (aOR) of 2.02 (95% confidence interval = 1.00-4.12, p = 0.05). Conclusion: Blood NLR may serve as a marker to predict the need for hospitalization due to bronchiectasis exacerbation.

Cardiovascular outcomes following hospitalisation for exacerbation of bronchiectasis: a territory-wide study.

BACKGROUND: Although bronchiectasis is reported to be associated with cardiovascular disease, evidence for an association with cardiovascular events (CVEs) is lacking. METHODS: A territory-wide retrospective cohort study was conducted in Hong Kong involving all patients who had bronchiectasis diagnosed in public hospitals and clinics between 1 January 1993 and 31 December 2017 were included. Patients were allocated to be exacerbator or non-exacerbator group based on hospitalzied bronchiecsis history and CVEs over the next 5 years determined. Propensity score matching was used to balance baseline characteristics. RESULTS: 10 714 bronchiectasis patients (mean age 69.6±14.4 years, 38.9% men), including 1230 in exacerbator group and 9484 in non-exacerbator group, were analysed. At 5 years, 113 (9.2%) subjects in the exacerbator group and 87 (7.1%) in the non-exacerbator group developed composite CVEs. After adjustment for age, sex, smoking and risk factors for cardiovascular disease, bronchiectasis exacerbation was associated with increased risks for acute myocardial infarction (AMI), congestive heart failure (CHF) and CVE compared with those in the non-exacerbator group with adjusted HR of 1.602 (95% CI 1.006-2.552, p value=0.047), 1.371 (95% CI 1.016-1.851, p value=0.039) and 1.238 (95% CI 1.001-1.532, p=0.049) in the whole cohort. Findings were similar for the propensity score-matched cohort for AMI and CVE. CONCLUSION: Patients who were hospitalised for exacerbation of bronchiectasis were at significantly increased risk of AMI, CHF and CVE over a 5-year follow-up period.

Salvage therapy beyond targeted therapy in lung adenocarcinoma.

Targeted therapy in lung adenocarcinoma has evolved rapidly over the last few years, especially in the application of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs). Although many patients with advanced EGFR-mutated or ALK-rearranged lung adenocarcinoma do benefit from treatment with a specific TKI, the duration of disease control is notoriously short. Different patterns of disease progression have been recognized that may require distinct treatment approaches. Isolated progressive disease in the central nervous system requires additional local therapy (radiotherapy or surgery) and an exploratory pulsatile regimen of TKI. Oligoprogressive disease at extracranial sites, representing resistant tumor clones in isolated lesions, requires local ablative therapy (radiotherapy or surgery) and continuation of the existing TKI. Multifocal progressive disease is a key therapeutic challenge to overcome because of widespread acquired resistance due to heterogeneous mechanisms. It is now known that EGFR TKI-acquired resistance is mostly (50-60%) due to a single resistance mutation in exon 20 (T790M) and occasionally (5-10%) due to c-MET amplification. On the contrary, the acquired resistance mechanisms to ALK TKI appear more diverse. Specific therapeutic strategies are being developed to overcome various acquired resistance mechanisms and may further improve the overall prognosis of advanced lung adenocarcinoma with actionable driver mutations.

Treatment outcomes in elderly with advanced-stage non-small cell lung cancer.

PURPOSE: Lung cancer remains the top cause of cancer morbidity and mortality in the world. Although the identification of epidermal growth factor receptor (EGFR) gene mutations could predict efficacy of tyrosine kinase inhibitor (TKI), testing for predictive biomarkers are not always possible due to tissue availability. The overall therapeutic decision remains a clinical one for a significant proportion of elderly patients with advanced stage lung cancer but no known EGFR mutation status. The purpose of this study was to compare the outcome of drug treatment modalities in progression-free survival (PFS) and overall survival (OS) for elderly with advanced-stage non-small cell lung cancer (NSCLC) and to identify clinical parameters that could predict treatment outcome. METHODS: Clinical records of patients aged 70 years or older with advanced-stage NSCLC who have received treatment were reviewed. A group of gender- and histology-matched subjects younger than age 70 years were identified as controls. RESULTS: Fifty-six elderly patients were included. The median age at diagnosis was 73 years; 60.7 % received only one line of treatment. Baseline performance status (PS) was the only predictor of improved PFS (p = 0.042) and OS (p = 0.002). There was no difference in survival between the upfront chemotherapy and the TKI groups CONCLUSIONS: In elderly with advanced-stage NSCLC without known EGFR mutation status, use of EGFR-TKI and chemotherapy resulted in comparable survival benefits. Age was not predictive of worse treatment outcome. The baseline PS should be taken into consideration in the therapeutic decision in elderly with NSCLC where the EGFR mutation status is not known.

Variability of Blood Eosinophil Count at Stable-State in Predicting Exacerbation Risk of Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) phenotyping using stable-state blood eosinophil level was shown to have prognostic implication in terms of exacerbation risk. However, using a single cut-off of blood eosinophil level to predict clinical outcome has been challenged. There have been suggestions that variability of blood eosinophil count at stable-state could provide additional information on exacerbation risk. Methods: A retrospective cohort study was conducted in a major regional hospital and a tertiary respiratory referral centre in Hong Kong, including 275 Chinese patients with COPD, to investigate the possible role of variability of blood eosinophil count at stable-state to predict COPD exacerbation risk in one year. Results: Higher variability of baseline eosinophil count, which is defined as the difference of the minimal and maximal eosinophil count at stable-state, was associated with increased risk of COPD exacerbation in the follow-up period with adjusted OR (aOR) of 1.001 (95% CI = 1.000-1.003, p-value = 0.050) for 1 unit (cells/µL) increase in variability of baseline eosinophil count, aOR of 1.72 (95% CI = 1.00-3.58, p-value = 0.050) for 1 SD increase in variability of baseline eosinophil count and aOR of 1.06 (95% CI = 1.00-1.13) for 50 cells/µL increase in variability of baseline eosinophil count. The AUC by ROC analysis was 0.862 (95% CI = 0.817-0.907, p-value < 0.001). The cut-off for variability of baseline eosinophil count identified was 50 cells/µL, with sensitivity of 82.9% and specificity of 79.3%. Similar findings were also shown in the subgroup with stable-state baseline eosinophil count below 300 cells/µL. Conclusion: Variability of baseline eosinophil count at stable-state might predict the exacerbation risk of COPD, exclusively among patients with baseline eosinophil count below 300 cells/µL. The cut-off value for variability was 50 cells/µValidation of the study findings in large scale prospective study would be meaningful.

Blood eosinophil percentage as a predictor of response to inhaled corticosteroid in bronchiectasis.

INTRODUCTION: The role of inhaled corticosteroid (ICS) among patients with bronchiectasis remains controversial. There is limited evidence of using baseline eosinophil count (absolute and percentage) as a marker to predict the role of ICS among patients with bronchiectasis. METHODS: A retrospective case-control study was conducted in a major regional hospital and tertiary respiratory referral centre in Hong Kong, including 140 Chinese patients with noncystic fibrosis (CF) bronchiectasis, to investigate the exacerbation risks of bronchiectasis among ICS users and nonusers with different baseline eosinophil counts. RESULTS: ICS user had significantly lower risk to develop bronchiectasis exacerbation with adjusted odds ratio (OR) of 0.461 (95% confidence interval [CI] 0.225-0.945, p-value 0.035). Univariate logistic regression was performed for different cut-offs of blood eosinophil count (by percentage) from 2% to 4% (with a 0.5% grid each time). Baseline eosinophil 3.5% was found to be the best cut-off among all with adjusted OR of 0.138 (95% CI = 0.023-0.822, p-value = 0.030). CONCLUSION: Baseline eosinophil count of 3.5% might serve as a marker to predict the benefits of ICS on exacerbation risk among patients with non-CF bronchiectasis.