Similarity of the tracheobronchial mucous glands and epithelium in infants with and without cystic fibrosis

doi:10.1016/S0046-8177(81)80240-7

Human Pathology

Volume 12, Issue 1, January 1981, Pages 36-48

https://doi.org/10.1016/S0046-8177(81)80240-7 Get rights and content

Abstract

A retrospective study of 90 infants and young children with cystic fibrosis and 90 age matched controls without cystic fibrosis revealed no essential histologic differences in their tracheobronchial mucous gland reactions with and without pulmonary infection. Although the secretory response to specific stimuli (especially Pseudomonas or staphylococcal infection) varied in individual cases, every change seen in cystic fibrosis was present in the controls. Inactive or normally active mucous glands were usually present in the cystic fibrosis and control infants in the absence of infection. Moderate mucous gland activity in the absence of overt infection was not pathognomonic of cystic fibrosis; it was seen in both groups in response to an irritative stimulus, such as aspirated blood or gastric contents. Mucous gland secretions contained both acid and neutral mucins in the presence of infection, with no real distinction between the cystic fibrosis infants and controls, differing from the predominantly acid mucins in infected polyps of older children. Reparative squamous metaplasia in the tracheobronchial tract occurred more frequently in infants with cystic fibrosis than in controls. Although cystic fibrosis did predispose to progressive pulmonary disease (bronchiolitis, bronchiectasis), similar lung lesions were found in other metabolic and chronic disorders.

References (8)

LambD. et al.
The tracheobronchial submucosal glands in cystic fibrosis: a qualitative and quantitative histochemical study
Br. J. Dis. Chest.
(1972)
EsterlyJ.R. et al.
Massive pulmonary hemorrhage in the newborn: pathologic considerations
J. Pediat.
(1966)
ZuelzerW.W. et al.
The pathogenesis of fibrocytic disease of the pancreas
Pediatrics
(1949)
EsterlyJ.R. et al.
Observations in cystic fibrosis of the pancreas: pulmonary lesions
Johns Hopkins Med. J.
(1968)

There are more references available in the full text version of this article.

Cited by (34)

Loss of ciliated cells and altered airway epithelial integrity in cystic fibrosis
2021, Journal of Cystic Fibrosis
Citation Excerpt :
The airway epithelium, intrinsically altered through the genetic defect in CFTR function, is therefore particularly exposed and its integrity is susceptible to be further affected by pathogens or other external agents [2]. Autopsy studies showed early pulmonary changes in CF patients such as bronchiectasis, squamous metaplasia or goblet cell hyperplasia [4–6]. More recently, different studies focused on epithelial specification in CF bronchial biopsies or lung explants, with increased proliferative zones and basal cell hyperplasia [7,8], glandular hyperplasia [8,9], and increased mucins-expressing cells [8,10].
In cystic fibrosis, the respiratory epithelium is the target tissue of both the genetic abnormality of the disease and of external aggressions, notably by pathogens (Pseudomonas aeruginosa). A detailed characterisation of the cystic fibrosis bronchial epithelium is however lacking, as most previous studies focused on the nasal epithelium or on cell lines. This study aimed to characterise the abnormal phenotype and epithelial-to-mesenchymal transition in cystic fibrosis bronchial epithelium and to evaluate in cell cultures whether abnormalities persist ex vivo.
Explant lung tissues (n = 44) were assessed for bronchial epithelial cell phenotyping by immunostaining. Human bronchial epithelial cells were derived from basal cells isolated from cystic fibrosis patients or control donors and cultured in air-liquid interface for 2, 4 or 6 weeks.
Enhanced mucin 5AC and decreased β-tubulin expression were observed in cystic fibrosis airways reflecting a decreased ciliated/goblet cell ratio, associated with increased number of vimentin-positive cells, indicating epithelial-to-mesenchymal transition process. These features were recapitulated in vitro, in cystic fibrosis-derived reconstituted epithelium. However, they were not induced by CFTR inhibition or Pseudomonas infection, and most abnormalities tended to disappear in long-term culture (6 weeks) except for increased fibronectin release, an epithelial-to-mesenchymal transition marker.
This study provides new insights into airway epithelial changes in cystic fibrosis, which are imprinted through an acquired mechanism that we could not relate to CFTR function.
Acidic Submucosal Gland pH and Elevated Protein Concentration Produce Abnormal Cystic Fibrosis Mucus
2020, Developmental Cell
Citation Excerpt :
When faced with a challenge from inhaled or aspirated material or pathogens, cholinergic stimulation induces submucosal glands to secrete abundant amounts of mucus (Ballard and Spadafora, 2007; Wine and Joo, 2004). Previous studies using pigs, which have submucosal glands like those of humans (Joo et al., 2010; Rogers et al., 2008a), revealed that after traveling up the submucosal gland duct, mucus emerges onto the airway surface in the form of strands (Ermund et al., 2017; Fischer et al., 2019; Oppenheimer, 1981; Ostedgaard et al., 2017; Simel et al., 1984; Trillo-Muyo et al., 2018). Beating cilia on surface epithelial cells pull mucus strands toward the larynx.
In response to respiratory insults, airway submucosal glands secrete copious mucus strands to increase mucociliary clearance and protect the lung. However, in cystic fibrosis, stimulating submucosal glands has the opposite effect, disrupting mucociliary transport. In cystic fibrosis (CF) pigs, loss of cystic fibrosis transmembrane conductance regulator (CFTR) anion channels produced submucosal gland mucus that was abnormally acidic with an increased protein concentration. To test whether these variables alter mucus, we produced a microfluidic model of submucosal glands using mucus vesicles from banana slugs. Acidic pH and increased protein concentration decreased mucus gel volume and increased mucus strand elasticity and tensile strength. However, once mucus strands were formed, changing pH or protein concentration largely failed to alter the biophysical properties. Likewise, raising pH or apical perfusion did not improve clearance of mucus strands from CF airways. These findings reveal mechanisms responsible for impaired mucociliary transport in CF and have important implications for potential treatments.
Cystic fibrosis
2019, Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics: Cardiovascular, Respiratory, and Gastrointestinal Disorders
Cystic fibrosis (CF) is one of the most common autosomal recessive disorders associated with decreased longevity in the Caucasian population. The disease is classically described as a triad; chronic obstructive pulmonary disease, exocrine pancreatic insufficiency, and elevation of chloride concentration in sweat. The underlying pathophysiology involves abnormal ion transport due to dysfunction of the CF transmembrane conductance regulator (CFTR). Altered salt and water movement across epithelia interferes with the hydration and ionic composition of mucus secretions. Abnormal mucus impairs clearance and defense systems, leading to inflammation and destruction of the lungs, the pancreas, and the developing vas deferens in males. The development of bioavailable small molecules that augment CFTR function is revolutionizing the treatment of CF.
Cystic Fibrosis
2013, Emery and Rimoin's Principles and Practice of Medical Genetics
The pathology of cystic fibrosis
2002, Current Diagnostic Pathology
Cystic fibrosis (CF) is one of the commonest lethal inherited conditions among Caucasians. It affects multiple organ systems and exhibits a range of clinical problems of varying severity. Life expectancy has improved in recent years as treatment regimes have become more intensive, but current treatments are expensive, often time consuming and may affect quality of life. New treatments for the pulmonary disease are under clinical trial and include antiproteases, amiloride, a sodium channel blocker, DNase and gene therapy. The gene for cystic fibrosis was identified in 1989 and this together with the emerging technology of gene therapy heralded a new dawn for the treatment of genetic disease. The lung is considered an ideal organ to target due to ease of access, but subsequent research has shown that the airway surface provides an efficient barrier to topically applied gene transfer agents. A number of Phase I clinical safety trials were carried out through the 1990s and provided proof of concept evidence that delivery of DNA by either viral or non-viral means was safe though not clinically efficacious. Current research is now focusing more on the barriers faced by delivery agents, with the aim that more efficient gene delivery will lead to a gene therapy for cystic fibrosis. The histopathologist is rarely called upon to make the initial diagnosis as cystic fibrosis is usually diagnosed clinically, being characterized by chronic bronchopulmonary infection, malabsorption due to pancreatic insufficiency and a high sweat-sodium concentration on sweat testing. Most information concerning both macroscopic and microscopic findings in cystic fibrosis has come from autopsy studies, so the pathological features are often extreme. However, with increasing survival of patients with cystic fibrosis, we are seeing more subtle changes in other organs and in addition, more aggressive drug therapy, gene therapy and lung transplantation are bringing with them new disease entities and complications.
Reversible pancreatic elastase-induced bronchial secretory cell metaplasia in the rat
1991, Experimental Pathology
Porcine pancreatic elastase (PPE) causes irreversible secretory cell metaplasia (SCM) in the intrapulmonary bronchi of hamsters. To determine whether this lesion can be induced in another rodent species, PPE was transorally instilled into the lungs of anesthetized rats. Saline-treated rats served as controls. Animals were killed 1 week, 3 weeks and 3 months after enzyme treatment and the lungs were inflation-fixed with 4% formalin/1% glutaraldehyde in 0.1 M Na cacodylate buffer at pH 7.4. Transverse sections from 3 intrapulmonary airway levels were embedded in paraffin and in glycol methacrylate. The secretory cell index (SCI) was determined from PAS-stained paraffin sections using a standardized scale of 0 to 4. There were no significant differences between SCI values of PPE-treated rats and saline-treated controls at any time point. Secretory cells in methacrylate sections were subclassified into S₁, S₂ and S₃ cells on the basis of increasing amounts of PAS-positive intracellular granules. At one week, there was no effect of PPE on airway level I secretory cells, but significant increases in numbers of S₂ and S₃ cells were seen in level II and in S₃ cells in level III. At 3 weeks, the number of S₁ cells were increased in level I and S₂ and S₃ cells were increased in level III; level II secretory cells were unaffected. Level III secretory cells had returned to normal by 3 months. There were no significant differences between treatment groups in the total number of secretory cells (S₁ + S₂ + S₃) at any airway level or time point examined. We conclude that a single intratracheal instillation of PPE causes mild SCM in rat intrapulmonary bronchi; recovery is complete by 3 months.

View all citing articles on Scopus

^**: This study was supported by SCOR grant 5-P50-HL-19157-02 from the National Heart, Lung and Blood Institute.

^*: Associate Professor of Pathology Emeritus, The Johns Hopkins University School of Medicine. Clinical Fellow, Johns Hopkins Hospital, Baltimore, Maryland.

View full text

Similarity of the tracheobronchial mucous glands and epithelium in infants with and without cystic fibrosis**

Abstract

Br. J. Dis. Chest.

J. Pediat.

The pathogenesis of fibrocytic disease of the pancreas

Pediatrics

Observations in cystic fibrosis of the pancreas: pulmonary lesions

Johns Hopkins Med. J.