Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (736 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Bronchiole; Terminal Bronchioles; Bronchioles, Terminal; Bronchiole, Terminal; Terminal Bronchiole; Respiratory Bronchioles; Bronchiole, Respiratory; Bronchioles, Respiratory.
Where it fits in the MeSH classification
- Broader topics
- Bronchi
Related concepts
- Bronchi
- Pulmonary Alveoli
Research landscape
PubMed indexes 602 records tagged with the MeSH heading “Bronchioles” (counts retrieved 2026-10-31). 108 of them (17.9%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 334 records.
Reviews account for 78 records (13.0%) and meta-analyses for 2. Randomized controlled trials number 2 (0.3%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 88 |
| 2000-2009 | 72 |
| 2010-2019 | 334 |
| 2020 onward | 108 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 78 | 13.0% |
| Meta-analyses | 2 | 0.3% |
| Randomized controlled trials | 2 | 0.3% |
Method: PubMed query "Bronchioles"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in anatomy and physiology
Anatomy describes how body structures are built and physiology describes how they normally work, so most findings here are descriptive or mechanistic rather than evidence about treatment. Much of what is known comes from dissection, imaging, tissue studies and experiments in animals, and measurements in healthy volunteers can differ from those in people with disease or at different ages. Normal ranges vary between individuals and populations. Check whether a result was measured in people or in another species, the age and health of the participants, and the method used.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells | 2009 | Research article Design not recorded in structured metadata | 149 | cc by PMID 20011520 · DOI · PMC2788414 |
| IL-33-ST2 axis regulates myeloid cell differentiation and activation enabling effective club cell regeneration | 2020 | Research article Design not recorded in structured metadata | 82 | cc by PMID 32963227 · DOI · PMC7508874 |
| Microbial volatile communication in human organotypic lung models | 2017 | Research article Design not recorded in structured metadata | 82 | cc by PMID 29176665 · DOI · PMC5701243 |
| Respiratory long COVID in aged hamsters features impaired lung function post-exercise with bronchiolization and fibrosis | 2025 | Research article Design not recorded in structured metadata | 9 | cc by PMID 40021627 · DOI · PMC11871369 |
Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The bronchioles of the murine lung are lined by a simple columnar epithelium composed of ciliated, Clara, and goblet cells that together mediate barrier function, mucociliary clearance and innate host defense, vital for pulmonary homeostasis.
- Closing excerpt
- Sox2 is required for proliferation and differentiation of Clara cells that serve as the progenitor cells from which Clara, ciliated, and goblet cells are derived.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (244 words)
The bronchioles of the murine lung are lined by a simple columnar epithelium composed of ciliated, Clara, and goblet cells that together mediate barrier function, mucociliary clearance and innate host defense, vital for pulmonary homeostasis. In the present work, we demonstrate that expression of Sox2 in Clara cells is required for the differentiation of ciliated, Clara, and goblet cells that line the bronchioles of the postnatal lung. The gene was selectively deleted in Clara cells utilizing Scgb1a1-Cre, causing the progressive loss of Sox2 in the bronchioles during perinatal and postnatal development. The rate of bronchiolar cell proliferation was decreased and associated with the formation of an undifferentiated, cuboidal-squamous epithelium lacking the expression of markers of Clara cells (Scgb1a1), ciliated cells (FoxJ1 and alpha-tubulin), and goblet cells (Spdef and Muc5AC). By adulthood, bronchiolar cell numbers were decreased and Sox2 was absent in extensive regions of the bronchiolar epithelium, at which time residual Sox2 expression was primarily restricted to selective niches of CGRP staining neuroepithelial cells. Allergen-induced goblet cell differentiation and mucus production was absent in the respiratory epithelium lacking Sox2. In vitro, Sox2 activated promoter-luciferase reporter constructs for differentiation markers characteristic of Clara, ciliated, and goblet cells, Scgb1a1, FoxJ1, and Agr2, respectively. Sox2 physically interacted with Smad3 and inhibited TGF-beta1/Smad3-mediated transcriptional activity in vitro, a pathway that negatively regulates proliferation. Sox2 is required for proliferation and differentiation of Clara cells that serve as the progenitor cells from which Clara, ciliated, and goblet cells are derived.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 20011520 · DOI · PMC2788414
IL-33-ST2 axis regulates myeloid cell differentiation and activation enabling effective club cell regeneration [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Evidence points to an indispensable function of macrophages in tissue regeneration, yet the underlying molecular mechanisms remain elusive.
- Closing excerpt
- Thus, the IL-33-ST2 axis controls epithelial niche regeneration by activating a large multi-cellular circuit, including monocyte differentiation into competent repairing AAMs, as well as group-2 innate lymphoid cell (ILC2)-mediated AAM activation.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (148 words)
Evidence points to an indispensable function of macrophages in tissue regeneration, yet the underlying molecular mechanisms remain elusive. Here we demonstrate a protective function for the IL-33-ST2 axis in bronchial epithelial repair, and implicate ST2 in myeloid cell differentiation. ST2 deficiency in mice leads to reduced lung myeloid cell infiltration, abnormal alternatively activated macrophage (AAM) function, and impaired epithelial repair post naphthalene-induced injury. Reconstitution of wild type (WT) AAMs to ST2-deficient mice completely restores bronchial re-epithelialization. Central to this mechanism is the direct effect of IL-33-ST2 signaling on monocyte/macrophage differentiation, self-renewal and repairing ability, as evidenced by the downregulation of key pathways regulating myeloid cell cycle, maturation and regenerative function of the epithelial niche in ST2-/- mice. Thus, the IL-33-ST2 axis controls epithelial niche regeneration by activating a large multi-cellular circuit, including monocyte differentiation into competent repairing AAMs, as well as group-2 innate lymphoid cell (ILC2)-mediated AAM activation.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32963227 · DOI · PMC7508874
Microbial volatile communication in human organotypic lung models [3]
Abstract reading summary — source excerpts
- Opening excerpt
- We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe, stable colonization of the host, or active disease.
- Closing excerpt
- Finally, we demonstrate multikingdom, volatile-mediated communication between the organotypic bronchiole and cultures of Aspergillus fumigatus and Pseudomonas aeruginosa.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (147 words)
We inhale respiratory pathogens continuously, and the subsequent signaling events between host and microbe are complex, ultimately resulting in clearance of the microbe, stable colonization of the host, or active disease. Traditional in vitro methods are ill-equipped to study these critical events in the context of the lung microenvironment. Here we introduce a microscale organotypic model of the human bronchiole for studying pulmonary infection. By leveraging microscale techniques, the model is designed to approximate the structure of the human bronchiole, containing airway, vascular, and extracellular matrix compartments. To complement direct infection of the organotypic bronchiole, we present a clickable extension that facilitates volatile compound communication between microbial populations and the host model. Using Aspergillus fumigatus, a respiratory pathogen, we characterize the inflammatory response of the organotypic bronchiole to infection. Finally, we demonstrate multikingdom, volatile-mediated communication between the organotypic bronchiole and cultures of Aspergillus fumigatus and Pseudomonas aeruginosa.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29176665 · DOI · PMC5701243
Respiratory long COVID in aged hamsters features impaired lung function post-exercise with bronchiolization and fibrosis [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Long-term consequences of SARS-CoV-2 infection affect millions of people and strain public health systems.
- Closing excerpt
- We postulate that pulmonary fibrosis and SCGB1A1+ club cell-rich areas of alveolar bronchiolization represent potential risk factors for other diseases in long-COVID survivors.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (197 words)
Long-term consequences of SARS-CoV-2 infection affect millions of people and strain public health systems. The underlying pathomechanisms remain unclear, necessitating further research in appropriate animal models. This study aimed to characterize the trajectory of lung regeneration over 112 days in the male hamster model by combining morphological, transcriptomic and functional readouts. We demonstrate that in the acute phase, SARS-CoV-2 Delta-infected, male, aged hamsters show a severe impairment of lung function at rest. In the chronic phase, similar impairments persisted up to 7 weeks post-infection but were only evident after exercise on a rodent treadmill. The male hamster model recapitulates chronic pulmonary fibrotic changes observed in many patients with respiratory long COVID, but lacks extra-pulmonary long-term lesions. We show that sub-pleural and interstitial pulmonary fibrosis as well as alveolar bronchiolization persist until 112 dpi. Interestingly, CK8+ alveolar differentiation intermediate (ADI) cells are becoming less prominent in the alveolar proliferation areas from 28 dpi on. Instead, CK14+ airway basal cells and SCGB1A1+ club cells, expressing cell proliferation markers, mainly populate alveolar bronchiolization areas at later time-points. We postulate that pulmonary fibrosis and SCGB1A1+ club cell-rich areas of alveolar bronchiolization represent potential risk factors for other diseases in long-COVID survivors.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40021627 · DOI · PMC11871369
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways [5]
- Research article Respiratory syncytial virus (RSV) and its propensity for causing bronchiolitis [6]
- Research article Clara cell: progenitor for the bronchiolar epithelium [7]
- Research article Small airway obstruction in COPD: new insights based on micro-CT imaging and MRI imaging [8]
- Research article The small airways and distal lung compartment in asthma and COPD: a time for reappraisal [9]
- Research article Pathophysiology of the small airways in chronic obstructive pulmonary disease [10]
References
- Tompkins DH, Besnard V, Lange AW, Wert SE, Keiser AR, Smith AN, et al.. Sox2 is required for maintenance and differentiation of bronchiolar Clara, ciliated, and goblet cells. . 2009. PMID 20011520 · DOI · PMC2788414
- Dagher R, Copenhaver AM, Besnard V, Berlin A, Hamidi F, Maret M, et al.. IL-33-ST2 axis regulates myeloid cell differentiation and activation enabling effective club cell regeneration. . 2020. PMID 32963227 · DOI · PMC7508874
- Barkal LJ, Procknow CL, Álvarez-García YR, Niu M, Jiménez-Torres JA, Brockman-Schneider RA, et al.. Microbial volatile communication in human organotypic lung models. . 2017. PMID 29176665 · DOI · PMC5701243
- Heydemann L, Ciurkiewicz M, Störk T, Zdora I, Hülskötter K, Gregor KM, et al.. Respiratory long COVID in aged hamsters features impaired lung function post-exercise with bronchiolization and fibrosis. . 2025. PMID 40021627 · DOI · PMC11871369
- Evans CM, Fingerlin TE, Schwarz MI, Lynch D, Kurche J, Warg L, et al.. Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways. Physiol Rev. 2016. PMID 27630174 · DOI · PMC5243224
- Pickles RJ, DeVincenzo JP. Respiratory syncytial virus (RSV) and its propensity for causing bronchiolitis. J Pathol. 2015. PMID 25302625 · DOI · PMC5638117
- Reynolds SD, Malkinson AM. Clara cell: progenitor for the bronchiolar epithelium. Int J Biochem Cell Biol. 2010. PMID 19747565 · DOI · PMC2787899
- Hogg JC, McDonough JE, Suzuki M. Small airway obstruction in COPD: new insights based on micro-CT imaging and MRI imaging. Chest. 2013. PMID 23648907 · DOI · PMC3653349
- Contoli M, Bousquet J, Fabbri LM, Magnussen H, Rabe KF, Siafakas NM, et al.. The small airways and distal lung compartment in asthma and COPD: a time for reappraisal. Allergy. 2010. PMID 19909298 · DOI
- Baraldo S, Turato G, Saetta M. Pathophysiology of the small airways in chronic obstructive pulmonary disease. Respiration. 2012. PMID 22868355 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.