Pulmonary alveolar proteinosis (PAP) is a rare pulmonary syndrome characterized by surfactant accumulation in the alveoli, which results in impaired gas exchange. There are three types of PAP: primary, secondary and congenital. Autoimmune PAP, which is under the category of primary PAP, is the most common form, and is caused by an impairment in granulocyte–macrophage colony-stimulating factor (GM-CSF) signalling, due to the presence of anti-GM-CSF autoantibodies. While some patients with PAP remain asymptomatic, most present with progressive dyspnoea of insidious onset that, rarely, can progress to respiratory failure and death. Currently, there is no known cure and no approved therapies for PAP. Whole-lung lavage remains the gold-standard treatment; however, several novel and promising targeted therapies are being actively investigated.
Treatments for chronic refractory cough that act centrally are not particularly effective and are often accompanied by adverse effects. A number of medications targeting purinergic receptors in vagal afferent nerves have recently been under investigation. One of them, gefapixant, has been approved for use in Japan and Switzerland. However, it has not been approved by the US Food and Drug Administration or the European Medicines Agency yet. Camlipixant, another drug in this class, is currently being studied in a phase III trial.
Cytisinicline is a naturally derived, plant-based medication that has been developed as a treatment for smoking cessation and nicotine dependence. Based on a product available in Europe, over 4 million smokers in Central and Eastern Europe have used this medication and over 10,000 subjects have participated in clinical trials worldwide. Cytisinicline acts as a partial agonist and partial antagonist for the alpha-4 beta-2 nicotinic acetylcholine receptors in the brain, which are the same receptors that are activated by nicotine. Cytisinicline helps to reduce cravings, withdrawal symptoms and the reward and satisfaction associated with smoking by preventing nicotine from binding to these receptors and releasing dopamine. The On-going Research of Cytisinicline for Addiction-1 clinical trial has shown that participants receiving 3.0 mg cytisinicline three times daily had the highest biochemically verified point-prevalence abstinence rate (50%) compared with placebo (10%) at the end of treatment, with no significant safety concerns. These quit results were statistically significant (p<0.001). Cytisinicline demonstrates weak binding to the 5-hydroxytryptamine 3 receptor that causes nausea, consistent with few observed nausea events in participants receiving cytisinicline. No new medications for tobacco dependence have received United States Food and Drug Administration approval since 2006. Cytisinicline represents a promising treatment for those globally who continue to smoke tobacco.
In this editorial, the American College of Chest Physicians (CHEST) guidelines for the respiratory management of patients with neuromuscular disease are discussed. The importance of personalizing treatment to the patient by using specific modalities of non-invasive ventilation is discussed, with emphasis on its benefits and the endpoints of successful treatment and the management of bulbar symptoms, such as secretion management and cough assistance. Finally, disease monitoring and the management of expectations throughout the course of the disease are explored.
Introduction: Refractory/unexplained chronic cough (RUCC) is a highly prevalent debilitating condition. The characteristics of RUCC suggest neuronal excitability. The biological mechanisms leading to this in humans are uncertain but are thought to involve changes in both the peripheral and central nervous system. Efficacy of P2X purinoceptor 3 (P2X3) antagonists suggests a role for extracellular adenosine triphosphate (ATP) in RUCC. In guinea pigs, ATP release occurs in response to hypotonic saline, through a transient receptor potential cation channel subfamily V member 4 (TRPV4)−ATP−P2X3 axis. Aims: In this review we discuss data from two European Respiratory Society 2022 abstracts in RUCC, as well as current insights and future directions in chronic cough. Results: We show that hypotonic saline cough challenge, measured by maximum evoked cough response, effectively discriminates RUCC from healthy volunteers. We show that low-dose morphine is efficacious in up to 75% of patients with RUCC and that side effects, experienced in around 38% of cases, can usually be managed. Further areas: We discuss treatable traits in chronic cough, existing pharmacological management options and future antitussives.
Obstructive sleep apnoea (OSA) is associated with reduced quality of life and increased risk of developing cardiovascular disease. The cornerstone parameter for diagnosing and assessing disease severity is the apnoea-hypopnea index (AHI); however, this index is insufficient for capturing the complexity of the disease. This is because AHI is poorly correlated to some of the major symptoms of OSA, excessive daytime sleepiness and risk of cardiovascular events. Thus, new and more personalized approaches, such as cluster analysis, are currently under investigation to better define individual patient risk of complications and optimize treatment benefits.
The carbon footprint of human activities is a conversation topic worldwide. Many fields, including healthcare, have attempted to reduce their carbon footprint. For example, in Canada, 4.6% of greenhouse gases are manufactured by healthcare institutions. When it comes to the accountable parties in healthcare, the current treatments for asthma and chronic obstructive pulmonary disease are the main contributors. These highly prevalent diseases affect 11% and 10% of the Western populations, respectively. This editorial aims to discuss the impact of pressurized metered dose inhalers on the environment, alternatives and changes to current diagnostic and therapeutic practices, public awareness, potential changes to regulations and paths forward.
The Journal of the Pan African Thoracic Society (JPATS) is an open-access peer-reviewed journal committed to publishing high-quality articles in the field of Pulmonology (adult and pediatric), Critical Care, Sleep, Thoracic Surgery.
Brensocatib is a reversible inhibitor of dipeptidyl peptidase 1, the enzyme that activates neutrophil serine proteases. In a phase II study in patients with bronchiectasis with frequent exacerbations, brensocatib was shown to reduce sputum elastase levels compared with placebo and, importantly, to reduce the number of pulmonary exacerbations and prolong the time to exacerbation without increasing infections or with significant side effects. A larger phase III study is underway and, if it confirms these findings, may pave the way for a novel treatment for bronchiectasis.
Ensifentrine is an inhaled ‘bifunctional’ dual phosphodiesterase 3/4 inhibitor that exhibits both bronchodilator and anti-inflammatory activities. Preclinical research has shown that ensifentrine can induce significant relaxation of human bronchi in vitro and suggested the possibility of a synergistic interaction between ensifentrine and β2-adrenoceptor agonists and, mainly, muscarinic receptor antagonists. Ensifentrine is the only dual phosphodiesterase 3/4 inhibitor under clinical development for the treatment of chronic obstructive pulmonary disease (COPD). It has been shown to induce bronchodilation, with a peak bronchodilator effect in patients with COPD similar to that seen after salbutamol administration, and anti-inflammatory activity in healthy individuals. Combined with standard bronchodilators (salbutamol, ipratropium or tiotropium), ensifentrine causes additional bronchodilation and, importantly, a significant reduction in hyperinflation in patients with stable moderate to severe COPD. A recent statement on the top-line phase III ENHANCE-2 study reported that ensifentrine induced significant bronchodilation and reduced the risk of moderate-to-severe COPD exacerbations in study participants. Ensifentrine continues to show promise as a novel drug for treating patients with COPD. Nevertheless, it is necessary to understand whether ensifentrine will be able to replace or reduce the use of currently available classes of bronchodilators, and/or whether it will be a valuable add-on therapy to the current standard of care to further optimize bronchodilation. Furthermore, it will be critical to clarify the anti-inflammatory profile of ensifentrine.
Interstitial lung disease is a leading complication of rheumatoid arthritis (RA). However, no drugs are yet available to treat these pulmonary and articular diseases together, although several agents show promise. Janus kinase inhibitors have found increasing favour among rheumatologists in the treatment of active RA because they can rapidly reduce articular disease activity and because they have a simple oral dosing regime and good patient acceptability. There are many plausible reasons to believe that Janus kinase inhibitors may delay the onset and improve the outcomes of RA-associated interstitial lung disease, in tandem with their beneficial articular effects. This editorial describes the rationale for exploring this possibility further.
People with severe corticosteroid-dependent asthma have greater morbidity, mortality and corticosteroid side effects than any other people with asthma. Just as type-2 inflammation and recurrent asthma attacks remodel airways, we propose the concept of ‘people remodelling’ to represent the utter disruption of people’s lives by the consequences of severe asthma and its associated corticosteroid treatments. To tackle this important problem, three biologics targeting type-2 inflammation – mepolizumab, benralizumab and dupilumab – have shown efficacy in tapering corticosteroids in dedicated phase III trials. We herein review the literature and propose an evidence-based, dose- and agent-specific corticosteroid weaning protocol for busy clinicians looking to achieve the best outcomes possible for their patients: independence from corticosteroids and reversal of people remodelling.
Low-dose computed tomography screening for lung cancer has led to the increased detection of peripheral pulmonary nodules (PPN). Bronchoscopic modalities of PPN biopsy (ultrathin bronchoscope, radial endobronchial ultrasound, electromagnetic navigational bronchoscopy) have not consistently shown diagnostic yields as high as ultrasound- or computed tomography-guided transthoracic needle aspiration or surgical lung biopsy. Robotic-assisted bronchoscopy gained US Food and Drug Administration approval in 2018 and 2019, and preliminary data have shown an improvement in the ability to navigate to PPN, obtain a diagnosis and evaluate tissue for molecular markers, all while maintaining a safety profile similar to that of traditional bronchoscopic methods. In this article, we aim to briefly summarize the data available on this novel technology and its potential for future applications.
With the increased prevalence of obesity worldwide, the incidence of obstructive sleep apnoea (OSA) has risen substantially. OSA is now also more commonly recognized within the pregnant population. The diagnosis of OSA during pregnancy is logistically difficult for many reasons. The symptoms of an uncomplicated pregnancy are traditionally believed to include sleep disruption and daytime sleepiness, without many specific data differentiating ‘normal’ from ‘pathological’, thus complicating the screening process for a true sleep disorder based on symptoms alone. Untreated OSA during pregnancy is associated with a variety of gestational health disorders, along with increased complications during delivery. Although screening protocols and increased healthcare provider awareness have led to earlier diagnosis and treatment of OSA in the general population, their implementation in the pregnant population is lacking. Studies on the use of continuous positive airway pressure in pregnancy have demonstrated its safety, but further research is needed to determine its benefits in this cohort.
Dexpramipexole offers a potential non-biologic option for patients with eosinophilic asthma in that it lowers blood eosinophil count and improves lung function parameters. However, longer-term studies in patients treated by reducing blood or tissue eosinophils, whether through biologics or oral therapies, are needed to better understand the role of the eosinophil in human biology and disease pathogenesis and to better delineate the clinical efficacy of Dexpramizole in asthma.
