Frontiers in Chronic Respiratory Diseases
The American Thoracic Society (ATS) International Conference 2026 concluded on May 20. The conference featured extensive discussion of research advances, precision diagnosis and treatment, and novel therapeutic strategies across respiratory medicine. Meanwhile, Chinese respiratory research teams continued to strengthen their capacity for original investigation and their international academic influence. This article highlights major advances in chronic respiratory diseases—specifically asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis—presented at ATS 2026.
I. Asthma: Precision Treatment, AI-Enabled Care, and Contributions from China
ATS 2026 showed that asthma management is evolving beyond its traditional focus on symptom control and prevention of exacerbations toward precision management centered on biomarkers, imaging phenotypes, omics signatures, and long-term outcomes. Compared with previous years, ATS 2026 placed greater emphasis on more ambitious treatment goals, clinical translation of artificial intelligence (AI), environmental health equity, and global asthma control. Chinese investigators also demonstrated substantially greater engagement and international visibility in research on asthma heterogeneity, mechanisms of eosinophilic inflammation, and precision phenotyping.
1. Biologics are shifting treatment goals from disease control to remission
In severe asthma, an expanding evidence base for targeted therapies—including anti-IgE, anti-IL-5, anti-IL-5 receptor, anti-IL-4 receptor, and anti-TSLP monoclonal antibodies—is moving treatment from empiric stepwise regimens toward endotype-guided care. “Clinical remission” emerged as a key concept at ATS 2026. It is no longer limited to symptomatic improvement, but encompasses a composite outcome of no exacerbations, no systemic corticosteroid use, well-controlled asthma, and stable or improved lung function. Some studies further proposed normalization of type 2 inflammatory biomarkers as a component of “complete remission.”
Several long-term follow-up and real-world studies suggested that patients who achieve clinical remission early after initiation of biologic therapy are more likely to maintain a lower risk of exacerbations, better disease control, higher lung-function levels, and reduced exposure to oral corticosteroids over the subsequent two to five years. Thus, the trend presented at ATS 2026 extends beyond simply increasing treatment options: the therapeutic goal for severe asthma is being upgraded from reducing exacerbations to achieving early remission, maintaining it over the long term, and reducing overall disease burden. Relevant expert discussions characterized the evolution of asthma treatment goals as a continuing progression from “cure” toward “reversal,” and noted that biologics may affect long-term airway structure and therefore have disease-modifying potential.
2. Disease modification and structural assessment are emerging frontiers
Airway remodeling is an important structural basis for persistent airflow limitation and poor treatment response in severe asthma. Studies presented at ATS 2026 showed improvements in mucus plug burden, airway-wall thickness, submucosal eosinophilic infiltration, and extracellular-matrix deposition in some patients with severe eosinophilic asthma after treatment targeting type 2 inflammatory pathways. These findings suggest that biologics may not only suppress inflammation but may also influence structural airway remodeling. Meanwhile, AI-enabled quantitative computed tomography (CT) is increasingly being used to longitudinally assess bronchial morphology, mucus plug volume, and air trapping, providing a more sensitive imaging tool for quantifying structural benefits after treatment. Whether airway remodeling can be reversed and disease progression modified will become an important dimension in evaluating the value of precision therapy for severe asthma.
3. Integration of AI and multiomics is advancing precision asthma research
AI was a major cutting-edge theme at ATS 2026. In asthma, its role is expanding from diagnostic support to imaging quantification, multiomics integration, risk prediction, and assessment of treatment response. AI-based quantitative CT can detect changes in mucus plugging, airway-wall thickness, and air trapping that are difficult to identify consistently by visual assessment. Combining AI with genomics, proteomics, metabolomics, and radiomics may facilitate identification of distinct inflammatory endotypes, disease trajectories, and patterns of therapeutic response. Sessions on AI and multiomics also emphasized that low-code and no-code analytical tools can lower technical barriers and help early- and mid-career investigators conduct translational research.
ATS 2026 also gave considerable attention to the ethics of AI. The use of AI in diagnosis, scientific writing, data analysis, and clinical decision support must address transparency, accountability, informed patient participation, privacy protection, algorithmic bias, and equity. For chronic respiratory diseases such as asthma, which is shaped by genetic, environmental, and social factors, AI should not merely improve efficiency; it should also support precise identification, early warning for high-risk patients, and health equity.
4. Environmental health and the global burden of asthma received substantial attention
Environmental health was another major theme in asthma at ATS 2026. Climate change, air pollution, extreme heat, increasing allergen exposure, wildfire smoke, and traffic-related pollution may all increase the risks of asthma development, symptom deterioration, and exacerbations. Findings from the CARDIA Lung Study further suggested that long-term exposure to wildfire-derived PM2.5 is associated not only with short-term respiratory events but also with subsequent obstructive ventilatory impairment, preserved ratio impaired spirometry (PRISm), and higher chronic lung disease–related proteomic risk scores, indicating that wildfire smoke may have persistent adverse effects on respiratory health.
The burden of asthma in low- and middle-income countries remains substantially underestimated. Limited access to diagnostic tools, underdiagnosis and misdiagnosis, inadequate availability and affordability of inhaled corticosteroids, and over-reliance on short-acting β2-agonists all contribute to uncontrolled asthma, severe exacerbations, and mortality. ATS 2026 emphasized that global asthma control must expand beyond pharmacotherapy to include standardized diagnosis, access to essential medicines, national asthma-management programs, and public-health interventions.
5. Contributions from China: from participation in international exchange to generation of original evidence
Chinese investigators made increasingly prominent contributions to research on asthma and eosinophilic inflammatory diseases at ATS 2026, with studies spanning genetic susceptibility, quantitative CT (qCT) clustering, sputum proteomics, mechanisms of eosinophilic granulomatosis with polyangiitis (EGPA), and sequential use of biologics. For example, an analysis based on the UK Biobank suggested that clonal hematopoiesis of indeterminate potential (CHIP) is associated with asthma risk, severity, and exacerbations. Research based on the Chinese C-BIOPRED cohort used qCT clustering and sputum proteomics to identify molecular pathways underlying distinct airway structural phenotypes. EGPA studies suggested that eosinophil extracellular traps (EETs) may serve as markers of disease activity and potential therapeutic targets.
These studies demonstrate that Chinese researchers are transitioning from participation in international academic exchange toward contributing local cohort data, formulating mechanistic questions, and strengthening the evidence base for precision phenotyping. With the continued development of international platforms such as ATS–China Day, the academic profile of Chinese respiratory medicine is expanding from the sharing of clinical experience to a more comprehensive presentation encompassing high-quality real-world research, translational medicine, and mechanistic investigation.
II. Chronic Obstructive Pulmonary Disease: Entering the Era of Precision Treatment
Chronic obstructive pulmonary disease (COPD) was a major topic in chronic airway disease at ATS 2026. Research placed greater emphasis on early identification, multidimensional diagnosis, imaging phenotypes, disease activity, and biomarker-guided precision treatment.
1. Early diagnosis: from a single spirometric criterion to multidimensional identification
Spirometry has long been the diagnostic gold standard for COPD, defined by a post-bronchodilator FEV1/FVC ratio below 0.70. However, a growing body of evidence indicates that the onset and progression of COPD precede the conventional spirometric diagnostic threshold. Some individuals with a history of smoking, biomass fuel exposure, or occupational exposure may already have respiratory symptoms, impaired quality of life, small-airway dysfunction, or structural abnormalities on chest CT even without established airflow limitation. Such individuals are often categorized as having pre-COPD or early COPD.
In 2025, the COPDGene 2025 Diagnosis Working Group and CanCOLD investigators proposed in JAMA a multidimensional diagnostic framework for COPD that integrates spirometry, symptoms, quality of life, manifestations of chronic bronchitis, and CT evidence of emphysema and airway-wall thickening. The study showed that this approach can identify individuals who are not diagnosed under conventional spirometric criteria but are at increased future risk of exacerbations, death, and lung-function decline. It can also reclassify some individuals with airflow limitation but no symptoms or structural abnormalities as not having COPD. As low-dose chest CT is increasingly used for lung-cancer screening and health examinations, imaging findings such as emphysema, small-airway disease, airway-wall thickening, and mucus plugs may provide important clues for early COPD identification and risk stratification.
2. Mucus plugs: from an imaging finding to a treatable trait
Mucus plugging remained a major focus of COPD research at ATS 2026. A mucus plug is not merely a symptomatic manifestation of chronic bronchitis; it is a structural pathological feature arising from the combined effects of mucus hypersecretion, impaired mucociliary clearance, airway inflammation, bacterial colonization, and small-airway obstruction. COPDGene data showed that mucus plugs occluding medium- and large-sized airways were associated with a higher risk of all-cause mortality in COPD, with risk increasing as more lung segments were involved. These findings indicate that mucus plugging is not only a localized airway abnormality but also an imaging marker of disease activity and adverse prognosis. A prospective Chinese cohort likewise demonstrated its clinical relevance: CT-detected mucus plugs were associated with an increased future risk of moderate or severe exacerbations, and mucus-plug burden showed a dose–response relationship with exacerbation risk. Involvement of four or more lung segments was associated with a markedly increased risk of subsequent exacerbations. Mucus plugging is therefore evolving from an “imaging phenomenon” into a “treatable trait” in precision COPD management. Interventional studies targeting mucus plugs may represent a new direction for preventing COPD exacerbations.
3. Biologics: COPD enters the era of inflammatory phenotype–guided treatment
COPD is not simply a neutrophilic inflammatory airway disease. Some patients have features of type 2 inflammation, including elevated blood eosinophil counts, activation of the IL-4/IL-13 pathway, IL-5–related eosinophilic inflammation, and increased release of epithelial alarmins. Recent breakthroughs in biologic therapies are moving COPD management beyond conventional inhaled medications toward precision treatment guided by inflammatory endotypes. Dupilumab, a fully human monoclonal antibody targeting the IL-4 receptor α subunit; mepolizumab, targeting interleukin-5; and benralizumab, targeting the IL-5 receptor α, have shown potential to reduce exacerbation risk in patients with elevated eosinophil counts and frequent exacerbations.
In addition to the IL-4/IL-13 and IL-5 pathways, epithelial alarmin pathways have become a focus of research. Tozorakimab is a novel monoclonal antibody targeting IL-33. The phase IIa FRONTIER-4 study enrolled patients with moderate-to-severe COPD and a chronic bronchitis phenotype and evaluated its effects on lung function, a composite exacerbation endpoint, symptoms, and biomarkers. Although the overall efficacy requires further confirmation, potential signals of benefit were observed in subgroups with a higher prior risk of exacerbations. In March 2026, the phase III OBERON and TITANIA trials both met their primary endpoints, suggesting that targeting the IL-33 pathway may provide a new strategy for preventing COPD exacerbations. Full results, however, require further evaluation after peer-reviewed publication.
Ensifentrine, an inhaled dual phosphodiesterase 3 and 4 inhibitor, combines bronchodilator and anti-inflammatory effects. The phase III ENHANCE-1 and ENHANCE-2 trials showed that nebulized ensifentrine improved lung function, symptoms, and quality of life and reduced the risk of exacerbations. The ENHANCE-CHINA study, led by the teams of Professors Pixin Ran and Yumin Zhou at the First Affiliated Hospital of Guangzhou Medical University, further confirmed its efficacy and safety in Chinese patients with COPD. Progress was also reported for novel PDE3/4 inhibitors developed in China. A study of TQC3721 led by Professor Weimin Li’s team at West China Hospital, Sichuan University, showed improvements in lung function and respiratory symptoms in patients with COPD.
4. Contributions from China: from participation in international exchange to generation of original evidence
Chinese investigators made increasingly prominent contributions to COPD research at ATS 2026, covering early diagnosis, mucus plugs, mechanisms of comorbidities, and the use of biologics.
The team of Professors Yongchang Sun and Xiaoyan Gai from Peking University Third Hospital presented molecular research on vascular endothelial injury and atherosclerosis mediated by extracellular vesicles derived from airway epithelial cells in COPD, as well as a prospective cohort study of long-term airflow limitation in post-tuberculosis lung disease. The work was presented in both oral and poster formats. Professor Sun also reviewed current topics including the use of biologics in Chinese patients with moderate-to-severe COPD. Professor Yahong Chen’s team presented a research on lipid nanoparticle delivery of HGF mRNA to promote lung-tissue repair in emphysema. Researchers from the First Affiliated Hospital of Guangzhou Medical University presented multiple studies, including findings from the COMPASS cohort and research on the definition of chronic bronchitis, expiratory central airway collapse and exacerbation risk, mucus plugs and the risk of exacerbations, simplified spirometric screening in primary care, and a quality-improvement program. Professor Ting Yang’s team from China–Japan Friendship Hospital presented an interim analysis of the BRIDGE-COPD study, while Professor Gang Hou’s team reported research on sarcopenia and frailty as comorbidities of COPD. Professor Yuanlin Song’s team from Zhongshan Hospital, Fudan University, presented findings showing that an emphysema phenotype was associated with a smaller improvement in lung function after triple therapy in patients with COPD. Several other Chinese respiratory experts and teams also delivered oral or poster presentations in the COPD field during ATS 2026.
Collectively, the COPD research presented at ATS 2026 points to three major shifts in COPD management. First, diagnosis is moving from reliance on a single spirometric threshold toward multidimensional identification integrating symptoms, imaging, and risk. Second, imaging phenotypes such as mucus plugging are becoming important markers of disease activity and exacerbation risk. Third, biologics and therapies with novel mechanisms are moving COPD into an era of precision treatment guided by inflammatory endotypes. Future priorities will be to identify high-risk populations earlier, define treatable traits more accurately, and focus treatment on reducing the risks of exacerbations and disease progression. China’s sustained activity and growing international influence in basic and clinical COPD research are expected to yield further high-quality original evidence and experience from China.
III. Pulmonary Fibrosis: Anti-fibrotic Therapy Enters a New Stage
1. The concept of progressive pulmonary fibrosis continues to evolve
Progressive pulmonary fibrosis (PPF) remained an important and extensively discussed topic across multiple sessions. A growing body of evidence suggests that different types of interstitial lung disease (ILD) may converge on common terminal fibrotic pathways.
The official ATS/ERS/JRS/ALAT clinical practice guideline on PPF remained an important reference standard during the conference. The definition of PPF was unchanged: within the past year, at least two of the following three criteria must be present, with no alternative explanation—worsening respiratory symptoms, radiological progression, and physiological progression.
2. Novel anti-fibrotic therapies
In addition to nintedanib and pirfenidone, the conference highlighted emerging mechanisms involving TGF-β, connective tissue growth factor (CTGF), integrins, and cellular-senescence pathways.
(1) TETON-1, a trial of inhaled treprostinil in idiopathic pulmonary fibrosis, was among the most closely watched breakthrough studies at the conference. In the phase III TETON-1 trial (RIN-PF-301), the primary endpoint showed a between-group difference in forced vital capacity (FVC) of 130.1 mL at 52 weeks in favor of inhaled treprostinil versus placebo (P<0.001). The effect emerged as early as week 8 and persisted through week 52. For secondary endpoints, the risk of clinical worsening was reduced by 33% (hazard ratio [HR], 0.67; P=0.0034), and the risk of acute exacerbation showed a numerical 50% relative reduction. Regarding safety, serious adverse events occurred less frequently in the treatment group than in the placebo group (18% vs 24%). A pooled analysis of TETON-1 and TETON-2 showed a more pronounced preservation of lung function, with a between-group FVC difference of 111.8 mL (P<0.0001). The risk of acute worsening of IPF was significantly reduced by 48% (HR, 0.52; P=0.0223), with significant improvements in quality-of-life scores and diffusing capacity of the lungs for carbon monoxide (DLCO). The TETON program demonstrated the therapeutic value of targeting pulmonary vascular remodeling and inflammatory pathways in IPF. Consistent benefits were observed both in patients receiving background nintedanib or pirfenidone and in those not receiving background antifibrotic therapy. The study was published concurrently in The New England Journal of Medicine.
(2) Other investigational drugs also reported updated findings:
Early data suggested that ENV-101, a smoothened (SMO) inhibitor, could significantly increase lung volume within 12 weeks.
Nerandomilast was shown to significantly slow lung-function decline and reduce mortality in patients with PPF, irrespective of concomitant background anti-fibrotic therapy.
TETON-PPF is a 52-week phase III extension study in PPF. It enrolled 698 participants with a diagnosis of PPF and more than 10% fibrosis. A partial interim description indicated that the participants enrolled to date had moderate restrictive impairment and that approximately half were receiving anti-fibrotic therapy.
3. AI-assisted assessment of interstitial lung disease
The use of AI for quantitative analysis of high-resolution CT and prediction of disease progression continued to expand.
(1) Moving screening upstream: deep learning for detecting “subclinical” ILD
Delayed diagnosis of ILD is an important contributor to poor outcomes. A key research trend in 2026 is the use of AI to identify early interstitial lung abnormalities (ILAs) on routine CT examinations.
(2) Although AI has substantial potential, important challenges remain, including algorithm generalizability across CT systems and hospitals, seamless integration with electronic medical record systems, and health-economic evaluation. Multimodal AI models integrating imaging, genomics, and clinical phenotypes are expected to become a central direction in precision medicine for ILD.
Conclusions and Outlook
ATS 2026 demonstrated that chronic respiratory diseases are rapidly entering a new stage of precision and AI-enabled medicine. Artificial intelligence, molecular monitoring, and precision therapies are profoundly reshaping the diagnosis and management of respiratory diseases. Meanwhile, the international influence of Chinese research teams continues to grow, and contributions from China are becoming an increasingly important part of global innovation in respiratory medicine.
About the Authors
Qingling Zhang
? Chief Physician, Professor, and Doctoral Supervisor, the First Affiliated Hospital of Guangzhou Medical University
? Head, Asthma Group, Chinese Thoracic Society
Xiaoyan Gai
? Chief Physician, Associate Professor, and Master’s Supervisor, Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital
? Member, Young Investigators Group, Chinese Thoracic Society
? Member-designate, Pulmonary Function Group, Chinese Thoracic Society
? Member, COPD Group, Respiratory Medicine Branch, Beijing Medical Association
Qianan Hu
? Attending Physician, China–Japan Friendship Hospital
? Academic profile: Author of multiple SCI-indexed articles in journals including Nature Communications and Advanced Science; principal investigator or participant in multiple national research projects.
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