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.

Implementation of evidence on management of pleural diseases: insights from a territory-wide survey of clinicians in Hong Kong.

BACKGROUND: Major advances in management of common pleural diseases have taken place in the past decade. However, pleural diseases are often managed by physicians of diverse training background and research on implementation of new knowledge is scanty. We aim to evaluate the practice pattern in pleural medicine among physicians in Hong Kong, for identification of possible gaps for clinical service improvement. METHODS: The Hong Kong Thoracic Society undertook a cross-sectional questionnaire survey in 2019, targeting clinicians of various subspecialties in internal medicine and levels of experience (basic and higher trainees, specialists) from twelve regional hospitals of diverse service scopes throughout Hong Kong. Respondents were selected by non-probability quota sampling. The questionnaire tool consisted of 46 questions covering diagnostic and therapeutic aspects of common pleural diseases. The responses were anonymous, and analysed independently using SPSS statistics software. RESULTS: The survey collected 129 responses, 47(36%) were from clinicians specialized in respiratory medicine. Majority of the respondents (98%) managed pleural diseases, including performing pleural procedures in their practice. Fifty-five percent of all the respondents had not received any formal training in transthoracic ultrasonography. A significant proportion of clinicians were unaware of pleuroscopy for investigation of exudative pleural effusion, indwelling pleural catheter for recurrent malignant pleural effusion, and combined intra-pleural Alteplase plus DNase for treatment of pleural infection (30%, 15% and 70% of non-respiratory clinicians respectively). Significant heterogeneity was found in the management of pleural infection, malignant pleural effusion and pneumothorax among respiratory versus non-respiratory clinicians. Contributing factors to the observed heterogeneity included lack of awareness or training, limited accessibility of drugs, devices, or dedicated service support. CONCLUSION: Significant heterogeneity in management of pleural diseases was observed among medical clinicians in Hong Kong. Continuous medical education and training provision for both specialists and non-specialists has to be strengthened to enhance the implementation of advances, improve quality and equity of healthcare provision in pleural medicine.

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.

Clinical efficacy and safety of pemetrexed with or without either Bevacizumab or Pembrolizumab in patients with metastatic nonsquamous non-small cell carcinoma.

BACKGROUND: Pemetrexed was approved by United States Food and Drug Administration (US FDA) in combination with platinum for the treatment of advanced nonsquamous non-small cell lung carcinoma (NSCLC) and malignant mesothelioma. Bevacizumab and pembrolizumab can be added to chemotherapy for patients with nonsquamous NSCLC with benefits but there has not been any dedicated head-to-head comparison between pembrolizumab-pemetrexed-platinum (PAC) and bevacizumab-pemetrexed-platinum (BAC) on their efficacy and safety. METHODS: This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 451 patients with advanced stage nonsquamous NSCLC that received first-line pemetrexed and platinum with or without bevacizumab or pembrolizumab. Patients who received pemetrexed-platinum (AC) were compared with those who received PAC and BAC. The primary endpoint was the progression-free survival (PFS). RESULTS: The median PFS for patients that received PAC was significantly longer than those who received BAC and AC (9 months vs. 6.8 months vs. 4.8 months, p < 0.05 among all three groups), with OR of 0.578 (95% CI, 0.343-0.976; p = 0.040) and 0.430 (95% CI, 0.273-0.675; p < 0.001) when compared to BAC and AC, respectively. Patients who received PAC also had a higher disease control rate and higher likelihood to receive continuation maintenance therapy than those on AC. There is no statistically significant difference in the grade 3 to 4 toxicity among the three treatment groups. CONCLUSIONS: Although both regimens are superior to pemetrexed-platinum alone, data from this retrospective single center study suggested a better PFS in  advanced stage nonsquamous NSCLC patient treated with first-line pembrolizumab-pemetrexed-platinum than bevacizumab-pemetrexed-platinum without an obvious increase in significant toxicity.

Risk factors of nephrotoxicity of maintenance pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung.

BACKGROUND: Nephrotoxicity is one of the concerns of prolonged maintenance therapy with pemetrexed. No reversible risk factors for pemetrexed-induced nephrotoxicity have been identified in previous studies. Identification of such factors would be clinically meaningful to maximize the chemotherapeutic benefits by avoiding premature termination of maintenance therapy which might otherwise result from the development of renal impairment. METHODS: This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 134 patients with advanced stage non-squamous NSCLC that received first line pemetrexed-platinum doublets followed by maintenance pemetrexed. The primary endpoint was the occurrence of nephrotoxicity. The risk factors of nephrotoxicity were identified. RESULTS: Presence of non-evacuated third-space fluid during treatment course (OR 4.185, 95% CI = 1.150-15.191, p-value 0.030), the use of cisplatin (instead of carboplatin) during the induction phase (OR 8.761, 95% CI = 1.684-45.577, p-value 0.010) and receiving more than 15 cycles of maintenance pemetrexed (OR 3.839, 95% CI = 1.022-14.413, p-value 0.046) were identified as independent risk factors to the development of nephrotoxicity associated with maintenance pemetrexed use. CONCLUSIONS: In order to reduce the risk of development of nephrotoxicity in NSCLC patient receiving first-line pemetrexed-platinum doublets, third-space fluid should be evacuated and carboplatin should be chosen over cisplatin whenever possible.

Haematological toxicity of pemetrexed in patients with metastatic non-squamous non-small cell carcinoma of lung with third-space fluid.

BACKGROUND: Pemetrexed was approved by United States Food and Drug Administration (US FDA) in combination with platinum for the treatment of advanced non-squamous non-small cell lung carcinoma (NSCLC) and malignant mesothelioma. Due to the structural similarity with methotrexate, there has been concern about the accumulation of pemetrexed in third space fluid that may result in increased toxicity. Previous small-scale studies have yet to conclusively prove this association. METHODS: This was a retrospective single-center cohort study conducted in Queen Mary Hospital in Hong Kong. The study included 329 patients with advanced stage non-squamous NSCLC that received first line pemetrexed and platinum. Patients who had non-evacuated third-space fluid, evacuated third-space fluid and without third-space fluid were compared. The primary endpoint was the occurrence of hematological toxicity. RESULTS: The presence of non-evacuated third-space fluid was shown to be associated with significantly more hematological toxicities, namely grade 3 or above hematological toxicities [Odd ratio (OR) = 2.450, p = 0.002], postponement of chemotherapy (OR = 3.837, p = 0.000) and need for dose adjustment (OR = 2.436, p = 0.022) when compared with those without third-space fluid. For patients with evacuated third-space fluid, these adverse effects were nullified. CONCLUSIONS: Presence of non-evacuated third-space fluid in patients with advanced non-squamous NSCLC predispose patients to significant hematological toxicity when pemetrexed and platinum chemotherapy is used. Evacuation of third-space fluid should be considered before starting pemetrexed and platinum doublet.

A 47-Year-Old Woman With Hemoptysis and a Lung Cyst.

CASE PRESENTATION: A 47-year-old woman was admitted to the hospital for an episode of hemoptysis. She coughed out small amount of clotted blood the morning of admission. She had no other symptoms on further review. Her medical history was unremarkable with the exception of an upper respiratory tract infection 9 months previously. She did not have any significant medical history or recent sick contacts. She was a lifelong nonsmoker and the mother of three teenaged children. She had irregular menses for the past 2 years, and her last menstrual period was 3 months ago. She reliably reported not engaging in any sexual contact for the past 2 years.

Real world experience on maintenance chemotherapy with gemcitabine in second line setting for advanced non-small cell lung carcinoma.

Maintenance chemotherapy was studied in first line setting for advanced stage non-small cell lung carcinoma (NSCLC). There has not been any data on the role of continuation maintenance chemotherapy in second line setting. A retrospective cohort study that included 226 patients with advanced stage NSCLC that received second line gemcitabine ± platinum was conducted. Patients who had continuation maintenance gemcitabine were compared with those who went on drug holiday. The primary endpoint was progression-free survival (PFS), counted from the end of induction therapy. The median PFS was significantly longer for patients who continued with maintenance gemcitabine when compared with those on drug holiday (5.6 vs 1.7 months, HR 0.392, p-value < 0.001). The overall survival was also significantly longer (21.4 vs 15.8 months, HR 0.508, p-value 0.047). There was no increase in incidence of adverse events for patients who underwent maintenance gemcitabine. Continuation maintenance therapy with gemcitabine in second line setting is a potentially feasible and safe option for patients with advanced NSCLC.

Significant reduction in hospital admissions for acute exacerbation of chronic obstructive pulmonary disease in Hong Kong during coronavirus disease 2019 pandemic.

BACKGROUND: Chronic respiratory diseases are risk factors for severe disease in coronavirus disease 2019 (COVID-19). Respiratory tract infection is one of the commonest causes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There has not been evidence suggesting the link between COVID-19 and AECOPD, especially in places with dramatic responses in infection control with universal masking and aggressive social distancing. METHODS: This is a retrospective study to assess the number of admissions of AECOPD in the first three months of 2020 in Queen Mary Hospital with reference to the admissions in past five years. Log-linear model was used for statistical inference of covariates, including percentage of masking, air quality health index and air temperature. RESULTS: The number of admissions for AECOPD significantly decreased by 44.0% (95% CI 36.4%-52.8%, p < 0.001) in the first three months of 2020 compared with the monthly average admission in 2015-2019. Compare to same period of previous years, AECOPD decreased by 1.0% with each percent of increased masking (p < 0.001) and decreased by 3.0% with increase in 1 °C in temperature (p = 0.045). The numbers of admissions for control diagnoses (heart failure, intestinal obstruction and iron deficiency anaemia) in the same period in 2020 were not reduced. CONCLUSIONS: The number of admissions for AECOPD decreased in first three months of 2020, compared with previous years. This was observed with increased masking percentage and social distancing in Hong Kong. We postulated universal masking and social distancing during COVID-19 pandemics both contributed in preventing respiratory tract infections hence AECOPD.

Respiratory arrest requiring resuscitation as a rare presentation of obstructive sleep apnoea and hypothyroidism.

A 79-year-old man, who had significant cardiovascular morbidities, presented with out-of-hospital respiratory arrest. He regained breathing after brief cardiopulmonary resuscitation by his paramedic son. After meticulous investigations, acute cardiovascular events and metabolic causes were ruled out while features of obstructive sleep apnoea were elicited. The findings on in-laboratory polysomnography were compatible with severe obstructive sleep apnoea, with unusually prolonged apnoea duration of up to 2.7 min which most likely accounts for the presentation as 'respiratory arrest'. Thyroid function test for investigation of his weight gain confirmed hypothyroidism. His symptoms improved gradually after positive airway pressure therapy with bi-level support and thyroxine replacement. On further evaluation, his hypothyroidism is believed to be a complication of long-term amiodarone exposure. The case highlights that the combination of obstructive sleep apnoea and hypothyroidism can lead to catastrophic manifestation and the unusually long apnoea could be a feature prompting further workup for possible hypothyroidism.