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[Series] Reframing remission in severe asthma: a conceptual framework for distinguishing disease activity versus damage

Remission is emerging as a feasible treatment goal in moderate-to-severe asthma, driven by the success of biologic therapies in controlling inflammation and reducing exacerbations. Yet current definitions of remission—focused on symptom control, lung function, and corticosteroid reduction—lack precision, can only be ascertained retrospectively, and do not reflect the underlying mechanisms and pathology that drive disease progression. This gap limits the clinical applicability of these definitions and might obscure opportunities for early, disease-modifying intervention.

[Series] Genetic and environmental risk factors for asthma: towards prevention

Asthma is a common chronic airway disease affecting an estimated 260 million individuals of all ages worldwide, contributing to substantial morbidity, mortality, and economic burden. Asthma is heterogeneous in age at onset (childhood vs adult onset), clinical presentation, type of underlying airway inflammation (type 2 high vs type 2 low), prognosis, and treatment response. Asthma is caused by multiple genetic and environmental factors, and possibly their interaction, across the life course. Genetic studies have provided important insights into the pathogenesis, biology, and immunology of asthma, fostering drug discovery.

[Articles] Assessment of the role of small airway dysfunction in relation to exacerbation risk in patients with well controlled asthma (ATLANTIS): an observational study

Recent surveys suggest that asthma remains inadequately controlled in more than 50% of adults with asthma despite guideline-based standard therapy. Small airways are often under-recognised as major sites of airway obstruction and inflammation. This might be related to lack of assessment with current tools such as impulse oscillometry, and thus under-treatment might explain inadequate control. Small airway dysfunction, which is common in adults with well controlled asthma, might represent an important biomarker of future risk of exacerbations.

[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.