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[Articles] Sweat chloride and lung function responses to elexacaftor–tezacaftor–ivacaftor in people with cystic fibrosis with two versus one responsive CFTR variants: an analysis of two real-world observational studies

People with cystic fibrosis with two responsive CFTR variants had a better correction of CFTR function in sweat glands after ETI initiation than those with only one responsive variant, but the response in terms of ppFEV1 was similar. These findings suggest that maximal improvement in lung function could be reached with current CFTR modulators and that no further increase in lung function would be expected from more potent restoration of CFTR function. Reaching normal lung function in people with cystic fibrosis and established lung disease might be limited by irreversible lung damage, suggesting that new therapeutic strategies aimed at improving lung function should be developed.

[Spotlight] Guy Brusselle: using hypothesis-driven and hypothesis-free research to aid people with asthma

Summer holidays spent hiking along the customs officers' trail, a long-distance walking route covering more than 2000 km of Brittany's coast, allow Guy Brusselle to indulge his passion for nature. That interest in the outdoors also influences his views on his career—Brusselle likens his work as Professor of Medicine at Ghent University in Belgium to a four-leaf clover, with each leaf representing an aspect of his role: clinical care, research, teaching, and outreach. “Four-leaf clovers are said to bring luck—for me, working as a clinician and researcher in a university hospital setting brings luck because I can combine those four domains in my work”, he smiles.

[Spotlight] Unique perspective on cystic fibrosis at Edinburgh Fringe

“I shouldn't be here”, said stand-up comedian Yvonne Hughes towards the start of her performance, before taking a step to her right. “I should be here instead”. The joke, which drew a suitably loud groan from her preview show's audience, epitomises the mix of comedy in Hughes' routine, juxtaposing the well-used phrase uttered by people who have defied doctors' expectations to survive, with a gag about not hitting the right mark on the stage. Hughes, 52, was diagnosed with cystic fibrosis when she was only a few months old, at a time when people with the condition were expected to only live into their early 20s.

[Correspondence] The rise of nicotine analogues in vaping products

Synthetic nicotine analogues are a new class of compounds making their way into the European and US vaping markets, raising urgent questions about public health, regulation, and scientific research.1 At the centre of this issue is 6-methyl nicotine. 6-methyl nicotine has attracted growing attention as a synthetic derivative that is promoted as an alternative to nicotine. The emergence of 6-methyl nicotine is no coincidence, but rather a direct consequence of the regulatory efforts targeting synthetic nicotine in the USA and Europe.

[Correspondence] Targeting pathogen adhesion molecules to improve COPD outcomes

Humans are programmed to follow intellectual fashions. In the field of chronic obstructive pulmonary disease (COPD), the concept that inflammation is the core problem is dominant, whereas other key issues such as parallel chronic infection and airway remodelling have received much less emphasis. In this Correspondence, we explain why specific microbes chronically colonise and infect the airways from a very early stage in COPD pathogenesis and discuss how it might be possible to stop this. These airway pathogens are likely major drivers of innate immune activation and oxidant production, which together with direct effects of cigarette smoke, lead to epithelial stem-cell gene reprogramming.

[Comment] Pooled testing for TB: revisiting a cost-saving innovation

Despite recent advances in screening and diagnosis, tuberculosis remains the deadliest infectious disease. An estimated 10·8 million people developed tuberculosis and 1·25 million died from it in 2023.1 Lagging investment in tuberculosis services and research is a major barrier to elimination. In 2023, of the US$22 billion annual funding target for tuberculosis care, only 26% of funding was available.1 Chronic underinvestment has led to limited and inequitable access to molecular WHO-recommended rapid diagnostics (mWRDs).

[Comment] Hedgehog signalling: on the way to curing idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease associated with poor quality of life, reduced survival, and substantial health-care use.1 Although the exact cause or causes of IPF remain unknown, our understanding of disease pathogenesis has improved substantially in the past 20 years. The current disease paradigm involves recurrent alveolar epithelial injury triggered by various factors, including genetic predisposition, environmental exposures, and ageing-related changes, followed by abnormal activation of fibroblasts and their differentiation to myofibroblasts, leading to excessive extracellular matrix production and lung remodelling.

[Comment] Inclusion of small airway dysfunction in asthma assessment and management: a place for impulse oscillometry?

In 1969, Ann Woolcock had already identified “The silent zone of the lung”1—ie, the small airways—as a vulnerable area for lung disease while remaining clinically silent. However, small airways are still neglected, despite being the major, and sometimes only, site of airway obstruction in asthma and chronic obstructive pulmonary disease.2 Small airway dysfunction can contribute to inadequate control, and asthma exacerbations remain a substantial problem, despite important advances in therapeutic possibilities.

[Comment] Relationship between CFTR variants, sweat chloride responses, and lung function improvements

Cystic fibrosis, the most common autosomal-recessive lung disease, was a deadly disease in infancy or early childhood for many centuries. Over the past seven to eight decades, symptomatic therapies have improved quality of life and reduced morbidity and mortality, thereby slowly increasing life expectancy to adulthood. Malfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein underlies cystic fibrosis. The introduction of CFTR modulator therapies, small molecules that improve the function of the CFTR protein, changed the face of cystic fibrosis to an unprecedented degree.

[Comment] Morphine for chronic breathlessness: time to say goodbye

The effect of chronic breathlessness on the lives of patients and their loved ones is tremendous, regardless of the underlying cause.1 Persistent breathlessness despite optimal treatment of the underlying disease is very common in chronic obstructive pulmonary disease (COPD), heart failure, cancer, and interstitial lung disease. Combined with the knowledge that the global burden of these diseases is still increasing,2 it seems nearly impossible to overstate the need for effective breathlessness treatments.

[Correspondence] Should pregabalin be regulated under the Narcotic Drugs and Psychotropic Substances (NDPS) Act of India?

Pregabalin is a gabapentinoid which was initially used as an adjuvant in antiepileptic treatment for partial seizures and later gained US FDA approval for its use in neuropathic pain in 2004.1 In India, Pregabalin is not included in Schedule H1 of the Drugs and Cosmetics Rules, which require strict monitoring and record-keeping of prescriptions to prevent abuse. It is also not considered a narcotic or psychotropic medication under India's NDPS Act. However, due to rising abuse, states like Telangana and Punjab have implemented prescription-only restrictions.

[Comment] A missing piece in Bangladesh's nutrition agenda: indigenous children and adolescents in the Chittagong Hill Tracts

Bangladesh has made strong progress in improving child survival and reducing malnutrition over the past two decades.1 However, not all communities have shared in this success. Indigenous children and adolescents living in the Chittagong Hill Tracts (CHT), a remote, hard-to-reach, hilly region in the southeast of the country, continue to face persistent health and nutrition inequalities2 that places them at serious risk.

[Viewpoint] Call to action: integrating steatotic liver disease into public health strategies in Canada

Steatotic liver disease (SLD), formerly known as fatty liver disease, is the most common chronic liver condition, affecting one in three people in the Americas, including Canada. Characterized by excess fat in the liver, SLD can progress from a benign state to advanced fibrosis and cirrhosis and is strongly linked to increased risks of cardiovascular disease, extra-hepatic cancers, and premature mortality. Despite its rising prevalence, SLD remains largely absent from Canada's public health agenda.

[Health Policy] Ensuring respiratory protection to improve population health, economic vitality, and national security

Respiratory protection decreases the risk of inhalation-related illnesses, but only if such protection is available, with a robust framework in place to support it. There are many current and potential inhalational hazards, and without adequate respiratory protection, these threaten not only health, but also economic prosperity and national security. The United States needs to build off existing expertise to implement a framework for respiratory protection of the entire populace. A recent National Academies of Sciences, Engineering and Medicine Report laid out detailed recommendations for such a framework, and there are steps that can be taken now.

[Health Policy] Firearm-related violence in the Caribbean is a complex systemic issue: how do we move towards a solution?

In the Caribbean, gun violence has reached crisis levels and regional heads of government have called for a public health approach to inform prevention and control. We describe the work of a multisectoral group convened to develop a “Pathway to Policy” to inform the regional approach. We utilized a systems mapping technique to inform our understanding of firearm-related crimes and injuries based on the expertise of stakeholders. The analysis is informed by publicly available data from thirteen countries of the Caribbean Community.