Speaker's Highlight

• Don Sin University of British Columbia, St. Paul Hospital (Canada)
  Kenneth R. Chapman Toronto General Hospital Research Institute (Canada)
• Parameswaran Nair McMaster University (Canada)
  Carolyn Calfee UCSF (U.S.A.)
• Gregory P. Downey University of Colorado School of Medicine (U.S.A.)
  David A. Schwartz University of Colorado School of Medicine (U.S.A.)
• Neil Schluger Tuberculosis Control Branch, California Department of Public Health (U.S.A.)
  Nick Kim Critical Care & Sleep Medicine, University of California San Diego (U.S.A.)
• Nicola Hananiah Baylor College of Medicine (U.S.A.)
  Jae-Joon Yim Seoul National University College of Medicine (Republic of Korea)
• Koichiro Asano Tokai University School of Medicine (Japan)
  Diahn-Warng Perng Taipei Veterans General Hospital (Taiwan)
• Konstantinos Kostikas University of Ioannina (Greece)
  Karin Klooster University Medical Center Groningen (Kingdom of the Netherlands)

• Airway remodeling in chronic asthma: mechanisms and reversibility

  Asthma is often described as a disease of variable bronchoconstriction, yet persistent inflammation can gradually alter the structure of the airway itself. This process, known as airway remodeling, helps explain why some patients continue to experience airflow limitation even when day-to-day symptoms appear controlled.

  Remodeling involves changes across the airway wall, including epithelial injury, thickening beneath the basement membrane, increased smooth-muscle mass, abnormal blood-vessel growth, and enlargement of mucus-producing glands. These changes can increase airway hyperresponsiveness and contribute to a progressive, partly fixed component of obstruction.

  Understanding which structural abnormalities can improve—and which may become more resistant to treatment—is central to modern respiratory medicine. The subject remains important for clinicians, researchers, and delegates attending scientific programs associated with APSR and KATRD.

  What airway remodeling means

  Airway remodeling is a collection of structural adaptations that develop after repeated cycles of inflammation, epithelial damage, repair, and bronchoconstriction. In chronic asthma, inflammatory cells such as eosinophils, mast cells, lymphocytes, and, in some phenotypes, neutrophils release mediators that influence fibroblasts, smooth-muscle cells, and epithelial tissue.

  The result is a thicker and less flexible airway wall. Subepithelial fibrosis can increase collagen deposition beneath the epithelium, while smooth-muscle hypertrophy and hyperplasia narrow the bronchial lumen during contraction. Goblet-cell metaplasia and mucous-gland enlargement may further impair airflow by increasing secretion volume and viscosity.

  Cellular and molecular drivers

  Repeated epithelial injury activates repair pathways that are useful in the short term but potentially harmful when stimulation persists. Damaged epithelial cells release alarmins such as thymic stromal lymphopoietin, interleukin-25, and interleukin-33. These signals can amplify type 2 inflammation, promote eosinophil survival, and encourage mucus production.

  Transforming growth factor beta is another important mediator. It stimulates fibroblast activity and extracellular-matrix deposition, contributing to reticular basement-membrane thickening. Vascular endothelial growth factor may support increased airway vascularity, while inflammatory mediators and mechanical stress can encourage airway smooth-muscle growth and altered contractility.

  Airway smooth muscle is more than a contractile tissue. It can release cytokines, chemokines, and growth factors, interact with immune cells, and influence the movement of inflammatory cells through the airway wall. This reciprocal relationship helps maintain bronchial hyperreactivity and may sustain disease activity even when acute symptoms are intermittent.

  How remodeling affects lung function

  Structural change can reduce the reversibility of airflow obstruction. A patient may still respond to a bronchodilator, but the improvement in forced expiratory volume may be smaller when fibrosis, muscle enlargement, mucus plugging, and wall thickening have become established. Remodeling can also reduce airway caliber at baseline, increasing the work required to breathe.

  The clinical pattern varies substantially. Some people with asthma retain near-normal lung function between exacerbations, while others develop persistent obstruction, air trapping, and reduced small-airway function. Longitudinal spirometry, bronchodilator testing, lung-volume measurement, and assessment of exacerbation history can help identify an evolving fixed component.

  Remodeling feature	Main biological effect	Potential clinical consequence	Reversibility
  Subepithelial fibrosis	Increased matrix deposition and wall stiffness	Persistent narrowing and reduced compliance	Often limited, especially when longstanding
  Smooth-muscle enlargement	Greater contractile force and airway sensitivity	Enhanced bronchoconstriction and hyperresponsiveness	May partially improve with sustained control
  Goblet-cell change	Excess mucus production	Cough, plugging, and variable obstruction	Can improve when inflammation is suppressed
  Vascular remodeling	Increased airway-wall blood flow and edema tendency	Wall thickening and inflammatory recruitment	Potentially modifiable, but evidence varies
  Epithelial dysfunction	Weakened barrier and abnormal repair	Greater sensitivity to allergens, viruses, and pollutants	Frequently improves with effective treatment

  Is airway remodeling reversible?

  Reversibility is best understood as a continuum rather than a simple yes-or-no outcome. Inflammation, mucus hypersecretion, epithelial dysfunction, and some degree of smooth-muscle activity may improve when asthma is treated consistently. Early intervention may prevent repeated injury from becoming a durable structural abnormality.

  Evidence suggests that inhaled corticosteroids can reduce airway inflammation, improve epithelial integrity, and limit some markers of subepithelial fibrosis. They may also reduce airway hyperresponsiveness and slow the decline in lung function. However, the extent of structural reversal differs among patients, and improvements may require sustained treatment over months or years.

  Biologic therapies targeting immunoglobulin E or type 2 inflammatory pathways can reduce exacerbations and inflammatory burden in selected severe asthma phenotypes. Whether these agents fully reverse established remodeling remains an active research question, although reductions in airway-wall thickness, mucus burden, or hyperresponsiveness have been reported in some studies.

  Treatment strategies that protect airway structure

  The most reliable approach is to suppress airway inflammation before structural abnormalities become entrenched. Controller therapy should be selected according to symptom pattern, exacerbation risk, lung function, comorbidities, inhaler technique, and adherence. Inhaled corticosteroid-containing regimens remain central for many patients, while combination therapy and biologics may be appropriate in more severe disease.

  Avoiding tobacco smoke, occupational sensitizers, indoor allergens, and severe pollution episodes can reduce repeated epithelial stress. Treatment of chronic rhinosinusitis, gastroesophageal reflux when clinically relevant, obesity, and obstructive sleep apnea may also improve overall asthma control and reduce inflammatory pressure on the lower airways.

  Asthma monitoring should extend beyond symptom frequency. Changes in spirometry, peak-flow variability, rescue medication use, exercise tolerance, and exacerbation patterns may reveal persistent disease activity. A stable symptom score does not always mean that airway inflammation or remodeling has stopped.

  Research priorities and clinical interpretation

  A major challenge is identifying remodeling early and measuring it without relying exclusively on invasive bronchial biopsy. High-resolution computed tomography, advanced lung-function testing, exhaled biomarkers, airway ultrasound, and magnetic resonance techniques may help characterize airway-wall changes. Standardized definitions are still needed so that studies can compare structural outcomes across asthma phenotypes.

  Future therapies may target fibrosis, abnormal smooth-muscle growth, epithelial repair, or matrix turnover directly. Precision medicine could also clarify which patients are most likely to benefit from anti-inflammatory treatment, biologic therapy, or emerging anti-remodeling agents. Combining clinical data with imaging and molecular biomarkers may make it possible to distinguish active, treatable remodeling from relatively fixed structural disease.

  For professionals planning to attend respiratory medicine discussions, practical details such as the registration guidelines can support participation in congress sessions where airway biology, severe asthma, and new therapeutic evidence are examined alongside broader healthcare priorities.

  Practical priorities for preserving lung function

  Early recognition and sustained control can reduce the likelihood that reversible inflammation will progress to persistent airway narrowing. A structured management approach should include:

  • Confirming the diagnosis and assessing alternative causes of fixed airflow limitation.
  • Reviewing inhaler technique and adherence at every appropriate clinical visit.
  • Using spirometry and other objective measures to track changes over time.
  • Treating comorbid allergic, upper-airway, metabolic, and sleep-related conditions.
  • Escalating therapy when exacerbations or persistent obstruction indicate uncontrolled disease.

  A personalized asthma action plan should explain controller use, reliever medication, exacerbation warning signs, and when urgent medical assessment is needed. This approach supports prevention rather than relying on repeated rescue treatment after airway injury has already occurred.

  Airway remodeling is a dynamic process shaped by inflammation, genetics, environmental exposure, treatment, and time. Continued attention to early diagnosis, objective monitoring, and targeted anti-inflammatory care can help preserve lung function and improve the prospects for structural recovery. Explore current respiratory medicine programs and evidence-based discussions to deepen understanding of how modern asthma care can change the course of chronic airway disease.

  Richard Russell Nuffield Department of Clinical Medicine, University of Oxford (United Kingdom)
• Mona Bafadhel King’s College London (United Kingdom)
  David Jackson Guy’s and St Thomas’ Hospital, King’s College London (United Kingdom)
• James Chalmers University of Dundee (United Kingdom)
  David Price University of Aberdeen (United Kingdom)