Gene editing is an ever-evolving field and Prime editing technology is among the latest ones. It makes it possible to modify a gene using a Cas9 nickase that cuts a single strand of DNA. This Cas9 nickase is fused with a reverse transcriptase that copies a single guide RNA synthetized by the researcher.
View Article and Find Full Text PDFAllergy Asthma Clin Immunol
April 2024
Background: Since the last guidance was published by the Canadian Thoracic Society, there have been several advances in the clinical management of severe asthma. To gain a better understanding of the current standards of care and treatment patterns of patients, the CASCADE practice reflective program was established to conduct a real-world analysis of severe asthma management among specialists in Canada with a goal of identifying areas of opportunity to enhance patient management and outcomes.
Methods: The CASCADE program was a two-part practice reflective and assessment program delivered through an on-line portal for selected specialists (Respirologists and Allergists) in Canada.
We report the first correction from prime editing a mutation in the gene, paving the way to gene therapies for RYR1-related myopathies. The gene codes for a calcium channel named Ryanodine receptor 1, which is expressed in skeletal muscle fibers. The failure of this channel causes muscle weakness in patients, which leads to motor disabilities.
View Article and Find Full Text PDFRationale: Severe asthma affects a small proportion of asthmatics but represents a significant healthcare challenge. Bronchial thermoplasty (BT) is an interventional treatment approach preconized for uncontrolled severe asthma after considering biologics therapy. It was showed that BT long-lastingly improves asthma control.
View Article and Find Full Text PDFMol Ther Nucleic Acids
December 2023
Therapeutic genome editing has the potential to cure diseases by directly correcting genetic mutations in tissues and cells. Recent progress in the CRISPR-Cas9 systems has led to breakthroughs in gene editing tools because of its high orthogonality, versatility, and efficiency. However, its safe and effective administration to target organs in patients is a major hurdle.
View Article and Find Full Text PDFIntroduction: Bronchial thermoplasty is an effective intervention to improve respiratory symptoms and to reduce the rate of exacerbations in uncontrolled severe asthma. A reduction in airway smooth muscle is arguably the most widely discussed mechanisms accounting for these clinical benefits. Yet, this smooth muscle reduction should also translate into an impaired response to bronchodilator drugs.
View Article and Find Full Text PDFInt J Chron Obstruct Pulmon Dis
September 2023
Introduction: Monoclonal antibodies targeting interleukin 5 (IL5) or its receptor (IL5R) are frequently used in severe asthma, in which they reduce exacerbations rate and oral corticosteroids (OCS) exposure. Anti-IL5/IL5Rs have been studied in patients with chronic obstructive pulmonary disease (COPD) without convincing benefits. However, these therapies have been used in clinical practice in COPD with apparently good results.
View Article and Find Full Text PDFJ Otolaryngol Head Neck Surg
April 2023
Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) often coexists with lower airway disease. With the overlap between upper and lower airway disease, optimal management of the upper airways is undertaken in conjunction with that of the lower airways. Biologic therapy with targeted activity within the Type 2 inflammatory pathway can improve the clinical signs and symptoms of both upper and lower airway diseases.
View Article and Find Full Text PDFGene therapy holds tremendous potential in the treatment of inherited diseases. Unlike traditional medicines, which only treat the symptoms, gene therapy has the potential to cure the disease by addressing the root of the problem: genetic mutations. The discovery of CRISPR/Cas9 in 2012 paved the way for the development of those therapies.
View Article and Find Full Text PDFAllergy Asthma Clin Immunol
February 2023
Background: In Canada, severe asthma affects an estimated 5-10% of people with asthma and is associated with frequent exacerbations, poor symptom control and significant morbidity from the disease itself, as well as the high dose inhaled, and systemic steroids used to treat it. Significant heterogeneity exists in service structure and patient access to severe asthma care, including access to biologic treatments. There appears to be over-reliance on short-acting beta agonists and frequent oral corticosteroid use, two indicators of uncontrolled asthma which can indicate undiagnosed or suboptimally treated severe asthma.
View Article and Find Full Text PDFPharmaceutics
October 2022
Gene therapy holds great promise in the treatment of genetic diseases. It is now possible to make DNA modifications using the CRISPR system. However, a major problem remains: the delivery of these CRISPR-derived technologies to specific organs.
View Article and Find Full Text PDFImmunol Allergy Clin North Am
August 2022
Much interest has been given to the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) in the past 2 decades, but the condition is still ill-defined. There is general agreement that a patient with longstanding asthma who develops fixed airflow obstruction after years of smoking has ACO although defining asthma in the face of COPD can be challenging. Many features of asthma are also found in patients with COPD without indicating an overlap and no consensus exists on which characteristics should be included in the definition of ACO.
View Article and Find Full Text PDFPurpose: Monoclonal antibodies targeting interleukin-5 (IL5) and its receptor (IL5R), used for severe asthma treatment, reduce eosinophils to almost complete depletion. Fractional exhaled nitric oxide (FeNO), a surrogate marker of eosinophilic airway inflammation, is expected to decrease after their initiation. Our center noticed increased FeNO levels in a few patients in whom anti-IL5/IL5R therapy was initiated.
View Article and Find Full Text PDFInt J Chron Obstruct Pulmon Dis
November 2021
Introduction: is an emerging Gram-negative MDR bacteria. In patients with chronic obstructive pulmonary disease (COPD), it is mostly found in those with severe exacerbation of COPD requiring mechanical ventilation. The significance of when detected in the sputum of ambulatory patients with COPD is uncertain.
View Article and Find Full Text PDFAlthough there is still no consensus on the definition of Asthma-COPD Overlap (ACO), it is generally accepted that some patients with airway disease have features of both asthma and COPD. Just as its constituents, ACO consists of different phenotypes, possibly depending on the predominance of the underlying asthma or COPD-associated pathophysiological mechanisms. The clinical picture is influenced by the development of airway inflammatory processes either eosinophilic, neutrophilic or mixed, in addition to glandular changes leading to mucus hypersecretion and a variety of other airway structural changes.
View Article and Find Full Text PDFTo identify candidate causal genes of asthma, we performed a genome-wide association study (GWAS) in UK Biobank on a broad asthma definition (n = 56,167 asthma cases and 352,255 controls). We then carried out functional mapping through transcriptome-wide association studies (TWAS) and Mendelian randomization in lung (n = 1,038) and blood (n = 31,684) tissues. The GWAS reveals 72 asthma-associated loci from 116 independent significant variants (P < 5.
View Article and Find Full Text PDFAsthma is a chronic inflammatory disease of the airways affecting more than 300 million patients worldwide. The disease can be of various severity ranging from very mild to severe. The severe form of the disease only affects about 5% of patients but is responsible for a large component of the overall disease burden and results in about half of direct asthma-related costs.
View Article and Find Full Text PDFJ Allergy Clin Immunol Pract
May 2021
Breathlessness during sport can be caused by various cardiorespiratory conditions, but when associated with stridor, usually arises from an upper airway etiology. The term exercise-induced laryngeal obstruction (EILO) is now used to describe the phenomenon of transient glottic closure occurring in association with physical activity. Exercise-related laryngeal closure is most commonly encountered in athletic individuals and likely affects between 5% and 7% of all young adults and adolescents.
View Article and Find Full Text PDFA 55-year-old former professional athlete reported out of proportion dyspnea on exertion. After a detailed cardiac investigation, a cardiopulmonary exercise test on an ergocycle demonstrated an abnormal and non-physiological ventilatory response characterized by a sharp rise in ventilation followed by a decrease while exercise workload was progressively increasing. This was accompanied by noisy breathing.
View Article and Find Full Text PDFLipoprotein lipase (LPL) is central to triglyceride metabolism. Severely compromised LPL activity causes familial chylomicronemia syndrome (FCS), which is associated with very high plasma triglyceride levels and increased risk of life-threatening pancreatitis. Currently, no approved pharmacological intervention can acutely lower plasma triglycerides in FCS.
View Article and Find Full Text PDFBackground And Objective: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk.
Methods: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma.
Background: Sampling of peripheral pulmonary nodules with radial endobronchial ultrasound (p-EBUS) increases diagnostic yield of bronchoscopy. However, diagnostic yield is influenced by numerous factors.
Objective: We evaluated the use of SpyGlass, a one millimeter diameter optic fiber, to obtain images of the distal mucosa and of pulmonary lesions detected with p-EBUS to determine if visual aspect of the distal mucosa was predictive of diagnosis.