Related Experiment Video

Updated: Mar 14, 2026

Bronchial Thermoplasty: A Novel Therapeutic Approach to Severe Asthma

Bronchial Thermoplasty: A Novel Therapeutic Approach to Severe Asthma

Published on: November 4, 2010

Constrictive Bronchiolitis in Cystic Fibrosis Adolescents with Refractory Pulmonary Decline

William T Harris¹, J Todd Boyd², Gary L McPhail³

¹1 Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama.

Annals of the American Thoracic Society

|September 30, 2016

Abstract

Rationale:

Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline.

Objectives:

To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy.

Methods:

Six adolescents with CF (mean age, 16.2 y; mean FEV₁, 52% predicted at biopsy) with significant pulmonary deterioration over 12-24 months (mean FEV₁ decline of 14% predicted/year) despite aggressive intervention underwent computed tomography imaging and ultimately lung biopsy to aid clinical management. In addition to routine clinical evaluation, histopathologic investigation included staining for transforming growth factor-β (TGF-β, a genetic modifier of CF lung disease), collagen deposition (a marker of fibrosis), elastin (to evaluate for bronchiectasis), and α-smooth muscle actin (to identify myofibroblasts).

Measurements And Main Results:

All computed tomography scans demonstrated a mix of bronchiectasis and hyperinflation that was variable across lung regions and within patients. Lung biopsy revealed significant peribronchiolar remodeling, particularly in patients with more advanced disease, with near complete obliteration of the peribronchiolar lumen (constrictive bronchiolitis). Myofibroblast differentiation (a TGF-β-dependent process) was prominent in specimens with significant airway remodeling.

Conclusions:

Constrictive bronchiolitis is widely present in the lung tissue of adolescents with CF with advanced disease and may contribute to impaired lung function that is refractory to conventional therapy (antibiotics, antiinflammatories, and mucolytics). TGF-β-dependent myofibroblast differentiation is prominent in areas of active fibrogenesis and may foster small airway remodeling in CF lung disease.

Keywords:

airway remodeling constrictive bronchiolitis cystic fibrosis myofibroblast transforming growth factor-β

More Related Videos

Implementation of Non-invasive Point of Care Transient Elastography for Evaluation of Liver Disease in Pediatric Populations with Cystic Fibrosis

Implementation of Non-invasive Point of Care Transient Elastography for Evaluation of Liver Disease in Pediatric Populations with Cystic Fibrosis

Published on: August 29, 2025

Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study

Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study

Published on: April 11, 2018

Related Concept Videos

Cystic Fibrosis: Management

Cystic Fibrosis: Management

Cystic fibrosis (CF) is an autosomal recessive disorder that predominantly affects individuals of Northern European descent, occurring at a rate of 1 in 3500. It is caused by a genetic mutation in a gene on chromosome 7, most commonly the ΔF508 mutation, that codes for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This results in thicker mucus secretions and obstruction pathologies in multiple organs, including the lungs and sinuses.
Sinus disease and chronic...

Cystic Fibrosis: Pathogenesis

Cystic Fibrosis: Pathogenesis

Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation

COPD: Management Using Bronchodilators and Corticosteroids

COPD: Management Using Bronchodilators and Corticosteroids

Chronic obstructive pulmonary isease (COPD) involves a group of progressive lung disorders characterized by persistent airflow limitation and chronic respiratory symptoms. Asthma-COPD Overlap Syndrome (ACOS), encompassing features of both asthma and Chronic obstructive pulmonary disease (COPD), is a group of progressive lung disorders that includes chronic bronchitis, emphysema, and refractory (non-reversible) asthma. ACOS leads to complex clinical presentations that combine the inflammatory...

Chronic Obstructive Pulmonary Disease-I: Introduction

Chronic Obstructive Pulmonary Disease-I: Introduction

Chronic Obstructive Pulmonary Disease (COPD) is a long-lasting respiratory condition requiring continuous attention and care. It is a progressive lung disease that leads to breathing challenges due to airflow obstruction. It manifests as persistent respiratory symptoms and restricted airflow resulting from abnormalities in the airways and alveoli, usually due to long-term exposure to harmful particles or gases. COPD mainly consists of two primary conditions: emphysema and chronic bronchitis.

Pulmonary Cycle: Exhalation

Pulmonary Cycle: Exhalation

In terms of human respiration, the act of expelling air, known as exhalation (or expiration), operates on the principle of pressure gradients. During expiration, the pressure within the lungs exceeds that of the surrounding atmosphere. Under normal conditions, quiet breathing involves passive exhalation and is free of muscular contractions. This is because the exhalation process is driven by the natural elastic recoil of the lungs and chest wall, both of which have an inherent tendency to...

Articles linked to this work by shared authors, journal, and citation graph.

High-grade urothelial carcinoma of the bladder in a 3-year-old boy: Complete resection and 18-year disease-free follow-up.

Urology case reports·2026

Patterns of weight gain during the first half of pregnancy and risk of large newborns in women with insulin-dependent diabetes mellitus.

Pregnancy (Hoboken, N.J.)·2026

Predicting Psychiatric Readmission of Children and Adolescents Using Machine Learning.

Journal of child and adolescent psychopharmacology·2026

Multi-Spectroscopic Determination of Exchange Coupling, Zero-Field Splitting, and g-Matrices in Radical-Bridged Dinuclear Fe(III) Complexes.

Inorganic chemistry·2026

Real-time prediction of rapid weight change in children with cystic fibrosis who have initiated modulator therapy.

Clinical nutrition ESPEN·2026

Resolving the inner versus outer component of the 5f radial wavefunction in the early actinides.

Chemical science·2026

See all related articles