Publications by authors named "Melanie Chin"

Article Synopsis
  • Elevated inflammation markers in cystic fibrosis (CF) patients can hinder lung function recovery after exacerbations; the study aimed to see if oral prednisone could help patients who weren’t improving with antibiotics.
  • A randomized trial with 173 CF patients tested the effectiveness of prednisone against a placebo after 7 days of antibiotic treatment, measuring recovery of lung function (FEV).
  • The results showed no significant difference in lung function recovery between the prednisone group (50% recovery) and the placebo group (39%), suggesting prednisone does not provide additional benefits for these patients.*
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Background: The COVID-19 pandemic led to global disruptions in non-urgent health services, affecting health outcomes of individuals with ambulatory-care-sensitive conditions (ACSCs).

Methods: We conducted a province-based study using Ontario health administrative data (Canada) to determine trends in outpatient visits and hospitalization rates (per 100,000 people) in the general adult population for seven ACSCs during the first pandemic year (March 2020-March 2021) compared to previous years (2016-2019), and how disruption in outpatient visits related to acute care use. ACSCs considered were chronic obstructive pulmonary disease (COPD), asthma, angina, congestive heart failure (CHF), hypertension, diabetes, and epilepsy.

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Importance: Frailty is associated with severe morbidity and mortality among people with chronic obstructive pulmonary disease (COPD). Interventions such as pulmonary rehabilitation can treat and reverse frailty, yet frailty is not routinely measured in pulmonary clinical practice. It is unclear how population-based administrative data tools to screen for frailty compare with standard bedside assessments in this population.

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Background: Frailty is a robust predictor of poor outcomes among patients with chronic obstructive pulmonary disease yet is not measured in routine practice. We determined barriers and facilitators to measuring frailty in a hospital setting, designed and implemented a frailty-focused education intervention, and measured accuracy of frailty screening before and after education.

Methods: We conducted a pilot cross-sectional mixed-methods study on an inpatient respiratory ward over 6 months.

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Article Synopsis
  • MOXIe was a two-part study that assessed the drug omaveloxolone for treating Friedreich's ataxia, a rare neurological disease, finding significant improvements in patient scores compared to a placebo.
  • The study included an open-label extension where patients previously on placebo were reassessed after receiving omaveloxolone, allowing for comparisons of their mFARS scores.
  • The results showed that the benefits of omaveloxolone persisted over time, indicating its positive impact on the disease's progression in affected patients.
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Background And Objectives: Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome.

Design, Setting, Participants, & Measurements: We randomly assigned patients with Alport syndrome, ages 12-70 years and eGFR 30-90 ml/min per 1.

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Background: The impact of the COVID-19 pandemic on the management of ambulatory care sensitive conditions (ACSCs) remains unknown.

Objectives: To compare observed and expected (projected based on previous years) trends in all-cause mortality and healthcare use for ACSCs in the first year of the pandemic (March 2020 to March 2021).

Design, Setting And Participants: We conducted a population-based study using provincial health administrative data on general adul population (Ontario, Canada).

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Improved treatments for cystic fibrosis (CF)-related lung disease have resulted in increased longevity, but also increased prevalence and severity of extrapulmonary manifestations of CF, treatment-related complications, age-related conditions, and psychosocial effects of longstanding chronic disease. Likewise, the recognition of mild CF phenotypes has changed the landscape of CF disease. This review outlines our current understanding of the common extrapulmonary complications of CF, as well as the changing landscape and future directions of the extrapulmonary complications experienced by patients with CF.

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Article Synopsis
  • - Alport syndrome is a rare genetic disorder affecting around 60,000 people in the USA and 103,000 in the EU, leading to progressive kidney failure and currently lacks approved specific treatments.
  • - The CARDINAL phase 3 study aims to assess the safety and effectiveness of bardoxolone methyl in patients aged 12-70 with confirmed Alport syndrome, randomized to either the drug or a placebo.
  • - Out of 371 screened patients, 157 were enrolled, mainly with a genetic diagnosis, average age of 39.2 years, and a baseline decline in kidney function despite many receiving other treatments, making this trial one of the largest of its kind.
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We describe a case of an otherwise healthy woman who presented with nonspecific respiratory symptoms, but was found to have recurrent focal findings on chest radiograph. Her CT scan showed an endobronchial lesion with distal bronchiectasis which was ultimately diagnosed as a mucoepidermoid carcinoma. In this report we discuss the clinical, radiographic, bronchoscopic and pathologic findings of rarely seen endobronchial mucoepidermoid tumors.

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Objective: Friedreich ataxia (FA) is a progressive genetic neurodegenerative disorder with no approved treatment. Omaveloxolone, an Nrf2 activator, improves mitochondrial function, restores redox balance, and reduces inflammation in models of FA. We investigated the safety and efficacy of omaveloxolone in patients with FA.

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Purpose Of Review: With improving life expectancy and quality of life, sexual and reproductive health (SRH) has become an increasingly important aspect of patient-centered cystic fibrosis care. This review aims to describe advances in cystic fibrosis-related SRH and highlight optimal practices.

Recent Findings: Recent publications suggest that people with cystic fibrosis follow a similar trajectory of sexual development and activity as their noncystic fibrosis peers, although contraception use is lower.

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In a multinational placebo-controlled phase III clinical trial in 2,185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, treatment with the Nrf2 activator bardoxolone methyl increased estimated glomerular filtration rate, a measure of kidney function, but also resulted in increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase. These increases in liver enzyme level(s) were maximal after 4 weeks of treatment and reversible, trending back toward baseline through week 48. Total bilirubin concentrations did not increase, and no cases met Hy's Law criteria, although two subjects had ALT concentrations that exceeded 10 × the upper limit of the population reference range leading to discontinuation of treatment.

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We describe the case of a previously healthy male patient who presented to a respiratory clinic with sinusitis, pulmonary cavities, and hemoptysis. Three weeks following a diagnosis of Granulomatosis with Polyangiitis (GPA) and initiation of immunosuppressive treatment, the patient suddenly developed a large pneumothorax that was complicated by empyema. In this report we discuss and highlight the rare pleural complications associated with GPA, and alert clinicians to monitor for these important complications even after disease-modifying treatment is initiated.

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Bardoxolone methyl attenuates inflammation by inducing nuclear factor erythroid-derived 2-related factor 2 and suppressing nuclear factor κB. The Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes (BEACON) trial was a phase 3 placebo-controlled, randomized, double-blind, parallel-group, international, multicenter trial in 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease. BEACON was terminated because of safety concerns, largely related to a significant increase in early heart failure events in patients randomized to bardoxolone methyl.

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Background: Treatment with bardoxolone methyl (Bard) in a multinational phase 3 trial, Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), resulted in increases in estimated glomerular filtration rate with concurrent reductions in serum magnesium. We analyzed data from several trials to characterize reductions in magnesium with Bard.

Methods: BEACON randomized patients (n = 2,185) with type 2 diabetes (T2DM) and stage 4 chronic kidney disease (CKD) 1:1 to receive Bard (20 mg) or placebo once daily.

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Background: Bardoxolone methyl has been shown to increase eGFR in several clinical trials, including a phase 3 trial in patients with type 2 diabetes and stage 4 CKD (BEACON), which was terminated early due to an increase in heart failure events in bardoxolone methyl-treated patients. A separate, "thorough QT" study was conducted in parallel with BEACON to evaluate the cardiovascular safety of bardoxolone methyl in healthy subjects.

Methods: Subjects in the "thorough QT" study were randomized to receive bardoxolone methyl 20 mg (therapeutic dose) or 80 mg (supratherapeutic dose), placebo, or moxifloxacin (400 mg; an active comparator).

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Background And Objective: Aerosol transmission of Pseudomonas aeruginosa has been suggested as a possible mode of respiratory infection spread in patients with cystic fibrosis (CF); however, whether this occurs in other suppurative lung diseases is unknown. Therefore, we aimed to determine if (i) patients with bronchiectasis (unrelated to CF) or chronic obstructive pulmonary disease (COPD) can aerosolize P. aeruginosa during coughing and (ii) if genetically indistinguishable (shared) P.

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Objective: Previous studies have demonstrated that suppression of Nrf2 in Friedreich ataxia tissues contributes to excess oxidative stress, mitochondrial dysfunction, and reduced ATP production. Omaveloxolone, an Nrf2 activator and NF-kB suppressor, targets dysfunctional inflammatory, metabolic, and bioenergetic pathways. The dose-ranging portion of this Phase 2 study assessed the safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia patients (NCT02255435).

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