Therapeutic and Mechanistic Advances in Chronic Cough.

Cough is one of the most common reasons patients seek medical care in the outpatient setting. Chronic cough (CC) in adults is defined as a cough lasting more than 8 weeks, with a global prevalence of approximately 10%. CC significantly impairs quality of life, affecting physical, social, and psychological well-being.

Protocol for bacterial filtration efficiency evaluations of facemask materials using viable bacteria-laden aerosol droplets.

Here, we present a protocol for determining the bacterial filtration efficiencies of facemask materials according to the American Society for Testing and Materials (ASTM) standard F2101-19. We describe steps for reproducibly generating, collecting, and enumerating viable bacteria-laden aerosols containing the bacterial pathogen Staphylococcus aureus. The optimized operating parameters generate 1,700 to 3,000 viable bacteria-laden aerosol droplets between 2.

The Clinical Approach to Chronic Cough.

Chronic cough remains a significant clinical challenge, affecting approximately 10% of the population and leading to significant impairment in psychological, social, and physical quality of life. In recent years, efforts have intensified to elucidate the mechanisms underlying chronic cough and to focus on investigating and treating refractory chronic cough (RCC). A "treatable trait" approach, which focuses on identifying and addressing the specific associated causes of chronic cough, has gained traction.

Unraveling the impact of operational parameters and environmental conditions on the quality of viable bacterial aerosols.

Viable pathogen-laden droplets of consistent quality are essential for reliably assessing the protection offered by facemasks against airborne infections. We identified a significant gap in guidance within standardized tests for evaluating the filtration efficiencies of facemask materials using viable bacteria-laden aerosol droplets. An aerosol platform, built according to the American Society for Testing and Materials standard F2101-19, was used to validate and standardize facemask filtration test procedures.

Generalizability of pharmaceutical randomized controlled trial eligibility criteria for progressive pulmonary fibrosis.

Background: Progressive pulmonary fibrosis (PFF) is of substantial interest for novel pharmacotherapy discovery, but little is known about clinical trial eligibility criteria. We evaluated eligibility criteria of PPF randomized controlled trials (RCTs), their representativeness in registry patients, and forced vital capacity (FVC) changes and mortality according to trial eligibility.

Methods: A systematic search was used to identify completed and in-progress phase II and III PPF RCTs.

Characterizing Hematological Changes Following Repeated Exposure to Non-Targeted Low-Dose Ionizing Radiation in Prostate Cancer Patients.

The duration and magnitude of haematological changes following non-targeted low-dose radiation have not been well explored. We previously reported that low-dose radiation (150 mGy 2x/week for 5 consecutive weeks) was well tolerated by participants (n = 15) with minimal toxicities and no changes in quality of life. Leukocytes, platelets and erythrocytes decreased from baseline measurement 12 months following treatment, however changes were not clinically significant.

The McMaster Cough Severity Questionnaire (MCSQ): a cough severity instrument for patients with refractory chronic cough.

Background: Cough severity represents an important endpoint to assess the impact of therapies for patients with refractory chronic cough (RCC).

Objective: To develop a new patient-reported outcome measure addressing cough severity in patients with RCC.

Methods: Phase 1 (item generation): A systematic survey, focus groups, and expert consultation generated 51 items.

Monocyte-driven inflamm-aging reduces intestinal barrier function in females.

Background: The intestinal barrier encompasses physical and immunological components that act to compartmentalize luminal contents, such as bacteria and endotoxins, from the host. It has been proposed that an age-related decline of intestinal barrier function may allow for the passage of luminal contents into the bloodstream, triggering a low-grade systemic inflammation termed inflamm-aging. Although there is mounting evidence to support this hypothesis in model species, it is unclear if this phenomenon occurs in humans.

Association between lung function and sleep disorder symptoms in a community-based multi-site case-finding study.

Obstructive airway disease is associated with sleep disturbances. We aimed to assess the relationship between lung function and sleep disorder symptoms using cross-sectionally collected data between March 2017 and August 2021 from the Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study, a prospective community-based multi-site case-finding study. Undiagnosed Chronic Obstructive Pulmonary Disease and Asthma Population study participants with respiratory symptoms but without diagnosed lung disease who completed spirometry and the Global Sleep Assessment Questionnaire were included.

The Effects of Diabetes on Gas Transfer Capacity, Lung Volumes, Muscle Strength, and Cardio-pulmonary Responses During Exercise.

Background: Diabetes is a risk factor for the development of vascular disease, chronic kidney disease, retinopathy, and neuropathy. Diabetes is a co-morbid condition commonly present in patients with respiratory disorders but the extent to which it influences ventilatory capacity, gas exchange, and functional capacity is not well known. Research question Does the presence of diabetes contribute to impairment in spirometry, gas transfer, and exercise capacity?

Methods: Retrospective analysis of all subjects who performed incremental cardio-pulmonary exercise testing (CPET) between 1988 and 2012 at McMaster University Medical Centre.

Modulating pro-fibrotic macrophages using yeast beta-glucan microparticles prepared by Pressurized Gas eXpanded liquid (PGX) Technology®.

Pro-fibrotic M2-like macrophages are widely implicated in the pathogenesis and progression of lung fibrosis due to their production of pro-fibrotic growth factors and cytokines. Yeast beta-glucan (YBG) microparticles have shown potential as immunomodulators that can convert macrophage polarization from a pro-fibrotic phenotype to an anti-fibrotic phenotype through the engagement of the Dectin-1 receptor. However, the processing conditions used to fabricate YBG microparticles can lead to unpredictable immunomodulatory effects.

Impact of Dyspnea on Adults With Respiratory Symptoms Without a Defined Diagnosis.

Background: We investigated dyspnea; its associated risk factors; and its impact on health care utilization, quality of life, and work productivity in adults with undiagnosed respiratory symptoms.

Research Question: What is the impact of dyspnea in adults with undiagnosed respiratory symptoms?

Study Design And Methods: This population-based study included 2,857 adults who were experiencing respiratory symptoms. These individuals had not been previously diagnosed with any lung conditions and were recruited from 17 Canadian centers using random digit dialing.

Effect of benralizumab on inflammation in skin after intradermal allergen challenge in patients with moderate-to-severe atopic dermatitis.

Background: Atopic dermatitis (AD) is a skin barrier dysfunction characterized by tissue eosinophilia.

Objective: In patients with AD, we evaluated the effect of eosinophil depletion with benralizumab on markers of inflammation in skin after intradermal allergen challenge.

Methods: A total of 20 patients with moderate-to-severe AD completed a randomized, double-blind, placebo-controlled parallel-group study comparing 3 doses of benralizumab (30 mg each) administered subcutaneously every 4 weeks (n = 9) with placebo (n = 11).

Chest CT Airway and Vascular Measurements in Females with COPD or Long-COVID.

Chest CT provides a way to quantify pulmonary airway and vascular tree measurements. In patients with COPD, CT airway measurement differences in females are concomitant with worse quality-of-life and other outcomes. CT total airway count (TAC), airway lumen area (LA), and wall thickness (WT) also differ in females with long-COVID.

Patient satisfaction with the management of refractory and unexplained chronic cough in Canada: Results from a national survey.

Background: Chronic cough (persisting for ≥8 weeks) is a common disorder affecting approximately 5 to 10% of adults worldwide that is sometimes refractory to treatment (refractory chronic cough [RCC]) or has no identifiable cause (unexplained chronic cough [UCC]). There is minimal information on the patient's experience of RCC/UCC in Canada. The aim of this study was to evaluate the patient journey and perceptions related to RCC/UCC management in Canada.

COVID-19 vaccine effectiveness among South Asians in Canada.

We evaluated the effectiveness of COVID-19 vaccines among South Asians living in Ontario, Canada compared to non-South Asians and compared the odds of symptomatic COVID-19 infection and related hospitalizations and deaths among non-vaccinated South Asians and non-South Asians. This was a test negative design study conducted in Ontario, Canada between December 14, 2020 and November 15, 2021. All eligible individuals >18 years with symptoms of COVID-19 were subdivided by ethnicity (South Asian vs other) and vaccination status (vaccinated versus not).

Cardiomyocyte crosstalk with endothelium modulates cardiac structure, function, and ischemia-reperfusion injury susceptibility through erythropoietin.

Erythropoietin (EPO) exerts non-canonical roles beyond erythropoiesis that are developmentally, structurally, and physiologically relevant for the heart as a paracrine factor. The role for paracrine EPO signalling and cellular crosstalk in the adult is uncertain. Here, we provided novel evidence showing cardiomyocyte restricted loss of function in in adult mice induced hyper-compensatory increases in expression by adjacent cardiac endothelial cells via HIF-2α independent mechanisms.

A Scoping Review of the Relationship Between Maternal BMI and Offspring Incidence of Respiratory Infection: Where Do We Go From Here?

Introduction: Pregnancy complications, including high maternal BMI, are associated with altered early development and child health outcomes. A growing body of work links the prenatal environment, specifically maternal BMI, with respiratory infections in offspring. In this rapid review, the authors review the literature supporting the hypothesis that high maternal BMI during pregnancy is associated with childhood respiratory infection incidence.

Efficacy of Biologics in Patients with Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Meta-Analysis.

Background: Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively.

Metatranscriptomic RNA-Seq Data Analysis of Virus-Infected Host Cells.

RNA sequencing (RNA-seq) analysis of virus-infected host cells enables researchers to study a wide range of phenomena involving host-virus interactions. This includes genomic analysis of the viral population itself, as well as analysis of the transcriptional dynamics of the virus and host during infection. In this chapter, we provide a guide for researchers interested in performing RNA-seq data analysis of virus-infected host cells or cell lines.

Nasal cathelicidin is expressed in early life and is increased during mild, but not severe respiratory syncytial virus infection.

Respiratory syncytial virus is the major cause of acute lower respiratory tract infections in young children, causing extensive mortality and morbidity globally, with limited therapeutic or preventative options. Cathelicidins are innate immune antimicrobial host defence peptides and have antiviral activity against RSV. However, upper respiratory tract cathelicidin expression and the relationship with host and environment factors in early life, are unknown.