State of the Art Pediatrics: Pediatric Pulmonology Year in Review 2025

As 2026 commences, we reflect on the advancements in pediatric pulmonology in 2025. There was an overall theme of improved and personalized treatment plans for children with chronic lung disease, such as cystic fibrosis (CF), bronchiectasis and asthma.

Care for children with CF continues to improve in the age of CFTR modulator therapies. These therapies are typically a combination of medications: correctors that help the CFTR protein to form the right shape to move to the cell surface, and potentiators that keep the CFTR chloride channel open. Next-generation CFTR modulators, also known as highly effective modulator therapies (HEMTs), typically include three different modulators. Recent studies extended Food and Drug Administration (FDA) market approval of elexacaftor/tezacaftor/ivacaftor (ETI, Kaftrio^TM or Trikafta^TM) for children as young as 2 years old. Improved clinical outcomes were found in over 80% of individuals with CF, and improvements were seen in sweat chloride and lung clearance index.¹ ETI was initially approved for individuals with at least one phe.508.del variant or other FDA-approved CFTR variant. A recent French study found ETI to be effective in over half of individuals without an FDA-approved CFTR variant.² Vanzacaftor/tezacaftor/deutivacaftor (VTD, brand name: Alyftrek^TM) was introduced as a once-a-day medication. Thus far, VTD has been shown in a phase 3 trial in children as young as age 6 to maintain FEV1 and to improve CFTR function.³ Commonly reported side effects of HEMTs include cold-like symptoms, gastrointestinal symptoms, elevated liver enzymes and elevated creatine phosphokinase. There have also been recent reports of neuropsychiatric side effects such as depression; interpretation is complicated by a known prevalence of depression and low mood in individuals with chronic disease, but these effects deserve further research.⁴

Recent research has changed our understanding of non-CF bronchiectasis. Bronchiectasis has long been regarded as incurable, but one study from Australia sought to challenge this notion. A review of high-resolution CT scans was done in 142 children without CF using the bronchoarterial ratio of >0.8. In this study, there was radiographic resolution of bronchiectasis in 40% of participants, improvement in 39%, and no change in 20%. On further analysis, those with positive Pseudomonas aeruginosa cultures did not show resolution, while those who did not culture P. aeruginosa, were of younger age at diagnosis, or had lower rates of exacerbations requiring IV antibiotics were more likely to show reversibility. Appropriate therapies included airway clearance therapies, immunomodulator therapy with azithromycin, and effective antibiotic treatment targeting cultured organisms.⁵ Azithromycin for immunomodulation in non-CF bronchiectasis has been studied, but it has been unclear how long azithromycin should be administered. One study in indigenous children in Australia found that long-term use of azithromycin was most effective between week 17 and week 62.⁶ The relevance of these findings for other populations has yet to be determined. Finally, brensocatib (Brinsupri^TM) is a first-in-class medication for non-CF bronchiectasis released in summer 2025 for individuals 12 years or older. Brensocatib works by blocking DPP1, an enzyme that activates inflammatory proteins in the lung, to decrease pulmonary exacerbations and improve lung function. Side effects have included gingival/periodontal concerns, hair loss, dry skin and rash.

In the field of asthma, biologic therapies have changed the lives of children with severe or refractory asthma. Phenotyping by type 2 (Th2) inflammatory markers, specifically fractional exhaled nitric oxide, absolute eosinophil counts, total serum IgE and allergen specific IgE, continues to be recommended as part of personalized asthma management. More biologics than ever are available for children and primarily target Th2 high asthma: omalizumab mepolizumab, benralizumab, dupilumab, and most recently tezepelumab. Of these, only tezepelumab is also approved for Th2 low asthma. All have good safety profiles, though patients show varying responses to different biologics consistent with the heterogeneity of asthma phenotypes. The ideal personalized choice of biologic for children with severe asthma continues to be limited by insurance and payor contingencies. For those interested, a review by Hillson, et al. delves into the complexities of asthma biologics beyond the scope of this summary.⁷

The 2025 annual edition of Global Initiative for Asthma (GINA) strategy report provided diagnostic criteria for asthma in children age 5 years and younger unlike previously suggested more predictive methods (e.g., modified Asthma Predictive Index).⁸ Clinicians can diagnose asthma in children 5 and younger who meet all three criteria: 1) recurrent acute episodes of wheezing with at least one acute episode of wheezing accompanied by asthma-like symptoms between episodes; 2) no other likely alternative cause of respiratory symptoms; and 3) timely clinical response of respiratory signs/symptoms to asthma treatment during an exacerbation (e.g., rapid response to short-acting beta2-agonist, oral corticosteroids) and decrease in frequency of acute wheezing episodes and/or symptoms in between episodes during a two- to three-month diagnostic trial of daily inhaled corticosteroids.

Finally, the effect of social disparities and climate change on asthma management remains troublesome as we leave 2025 behind. Severe and extreme weather events and environmental disasters (e.g., heat waves, cold spells, rapid weather changes, wildfire smoke) continue to be a challenge for our patients with asthma and chronic lung disease. Climate change disasters may affect local resources by disrupting medical care or worsening air pollutants. Worsening air quality, climate change and diminishing resources for those who are at the periphery continue to be a cause of morbidity and mortality for our most vulnerable patients.^9,10 So, as we enter 2026, may we all find the light within us to keep up the good fight and breathe easy!

References:

1. Goralski JL, Hoppe JE, Mall MA, et al. Phase 3 open-label clinical trial of ETI in children aged 2-5 years with CF and at least one F508del Am J Respir Crit Care Med. 2023;208(1):59-67.
2. Burgel PR, Sermet-Gaudelus I, Girodon E, et al. The expanded French compassionate programme for elexacaftor–tezacaftor–ivacaftor use in people with cystic fibrosis without a F508del CFTR variant: a real-world study. Lancet Respir Med. 2024;12(11):888-900.
3. Hoppe JE, Kasi AS, Pittman JE, et al. Vanzacaftor–tezacaftor–deutivacaftor for children aged 6–11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial. Lancet Respir Med. 2025;13(3):244-255.
4. VanElzakker MB, Tillman EM, Yonker LM, Ratai EM, Georgiopoulos AM. Neuropsychiatric adverse effects from CFTR modulators deserve a serious research effort. Curr Opin Pulm Med. 2023;29(6):603-609. PMID: 37655981. PMCID: PMC10552811. doi:10.1097/MCP.0000000000001014
5. Mills DR, Masters IB, Yerkovich ST, et al. Radiographic outcomes in pediatric bronchiectasis and factors associated with reversibility. Am J Respir Crit Care Med. 2024;210(1):97-107.
6. Vicendese D, Yerkovich S, Grimwood K, et al. Long-term azithromycin in children with bronchiectasis unrelated to cystic fibrosis: treatment effects over time. 2023;163(1):52-63.
7. Hillson K, Saglani S, Bush A. The new biologic drugs: Which children with asthma should get what? Pediatr Pulmonol. 2024;59(12):3057-3074.
8. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2025. https://ginasthma.org/2025-gina-strategy-report/
9. Lo D, Lawson C, Gillies C, et al. Association between socioeconomic deprivation, ethnicity and health outcomes in preschool children with recurrent wheeze in England: a retrospective cohort study. Thorax. 2024;79(11):1050-1059.
10. Bush A, Byrnes CA, Chan KC, et al. Social determinants of respiratory health from birth: still of concern in the 21st century? Eur Respir Rev. 2024;33(172):230222.