Elsevier

Archives of Oral Biology

Volume 60, Issue 11, November 2015, Pages 1650-1654
Archives of Oral Biology

Salivary flow rate and biochemical composition analysis in stimulated whole saliva of children with cystic fibrosis

https://doi.org/10.1016/j.archoralbio.2015.08.007Get rights and content

Highlights

  • Children with cystic fibrosis have salivary changes compared to to children without the disease.

  • Children with cystic fibrosis have reduced salivary flow rate.

  • Children with cystic fibrosis have reduced amylase and peroxidase activities.

  • Children with cystic fibrosis have reduced sialic acid concentration.

  • Children with cystic fibrosis have increased total protein concentration.

Abstract

Objective

It is recognized that cystic fibrosis (CF) patients present a risk for oral diseases, since it affects exocrine glands, and the treatment consists of a carbohydrate-rich diet. Recognizing the protective function of saliva on maintaining oral health, the aim of the study was to evaluate salivary parameters in stimulated whole saliva from children with CF.

Methods

A case-control study was conducted comparing stimulated whole saliva of healthy (n = 28; control group) and CF children (n = 21; experimental group). Salivary flow rate, initial pH, buffer capacity (total and in each range of pH), total protein and sialic acid (total, free, and conjugated) concentration, α-amylase and salivary peroxidase activities were evaluated. Data were compared by two-tailed Student t test (95% CI; p  0.05).

Results

CF patients presented a significant reduction in salivary parameters compared with the control group (p  0.05): salivary flow rate (36%), buffer capacity (pH range from 6.9 to 6.0), sialic acid concentration (total 75%, free 61%, and conjugated 83%); α-amylase and salivary peroxidase activities (55%). Additionally, a significant increase in total protein concentration (180%) of stimulated whole saliva from CF patients was verified compared with the control group (p  0.05).

Conclusion

Children with CF presented significant changes in salivary composition, including salivary flow rate, buffering capacity and protective proteins of the oral cavity, compared with children without CF.

Introduction

Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder caused by a variant in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The degree of CFTR dysfunction correlates with clinical features and can create phenotypes other than cystic fibrosis (Cutting, 2015). Individuals with cystic fibrosis show a high degree of variability in disease severity, complications and survival (Dodge, Lewis, Stanton, & Wilsher, 2007). The organs in which clinical abnormalities have been documented most in CF are the airways, pancreas and exocrine glands (Grody, 1999). A defective electrolyte transport in epithelial cells and viscous mucus secretions from glands and epithelia characterize this disorder, considered as a disease of fluid transport in epithelia that normally require passive, electroconductive transport of Cl−1 (Quinton, 1990).

Patients with cystic fibrosis can present a risk for oral diseases, since the treatment consists of a carbohydrate-rich diet, use of sugary drugs, mucolytics, and more frequent meals and food supplements. On the other hand, Narang, Maguire, Nunn and Bush, (2003) argued that the use of long term antibiotics and pancreatic enzymes may grant some protection against the development and progression of dental caries in these patients. Kinirons (1983) observed a reduction in dental caries prevalence among CF patients, suggesting that there was a link between altered saliva properties and low caries experience, but he reported no relation between the changes in saliva and the severity of the disease process. Enamel defects, particularly enamel opacities, which can be disfiguring, are more common in CF patients, but the occurrence of opacities may also be related to other conditions, such as prematurity, low birth weight, and ingestion of fluoridated toothpaste (Azevedo, Feijó, & Bezerra, 2006).

These identified risk factors, added to the lack of studies dealing with the impact of cystic fibrosis on children’s oral health, suggested the evaluation of certain biochemical parameters of stimulated whole saliva that present protective properties. This is most frequently studied substance for evaluating systemic disorders, as it is considered a noninvasive method that can be collected from individuals with modest training, using simple equipment, and hence provides a cost-effective approach for population screening (Deepa & Thirrunavukkarasu, 2010).

The saliva of CF affected patients contains increased levels of calcium and proteins, resulting in the formation of insoluble calcium-protein complexes that could compromise the function of salivary enzymes (Blomfield, Rush, Allars, & Brown, 1976), as well as increases in the salivary concentrations of sodium, phosphate, chloride, lipid and PGE2 (Rigas, Korenberg, Merrill, & Levine, 1989). A study showed changes in inorganic parameters of whole saliva from patients with CF, particularly increased chlorine, potassium and sodium, and reduced salivary flow rate (Gonçalves et al., 2013). However, there is a lack of reports concerning organic salivary parameters with protective, antioxidant, antimicrobial and digestive properties.

Previous studies on salivary aspects of patients with cystic fibrosis focused the inorganic composition of saliva (Blomfield et al., 1976, Gonçalves et al., 2013, Rigas et al., 1989). There is a lack of studies showing also organic aspects of saliva with different protective functions in the oral cavity. So, this study was planned with the aim to evaluate salivary parameters in stimulated whole saliva of children with cystic fibrosis (case) compared with healthy children (control), including salivary flow rate, buffer capacity, sialic acid concentration, α-amylase and salivary peroxidase activities, and total protein concentration.

Section snippets

Participants

This case-control study was conducted among CF children from the Public Hospital ‘Santa Casa de Misericórdia de São Paulo’, SP, Brazil (case group). All the children in attendance were invited to participate of the study (convenience sample). Considering ethics and exclusion criterias, final sample comprised 21CF children. Control group was matched by sociodemographics characteristics, with 28 children enrolled at a Public School, “Colégio Arnoso Costa’, located in a neighborhood near to the

Results

The sample presented 49 children, 28 CF children in Group 1 (52.4% boys and 47.6% girls; mean age = 9.09 ± 2.14), and 21 children without CF in Group 2 (35.7% boys and 64.3% girls; mean age = 9.04 ± 2.08). All participants of Group 1 used medical prescriptions that combined dornase alfa, pancreatic enzymes and fat-soluble vitamins (A, D, E and K) ingested in capsules.

All patients had Sweat Conductivity Equivalent NaCl (mmol/L) above 50 mmol/L. The results for FEV1 (% predicted) were 87.56 ± 25.37, 84.0

Discussion

It is recognized that CF patients present a risk for oral diseases, since the disease affects exocrine glands, with defective secretion of electrolyte and proteins by epithelial cells. The CF children of this study presented significant changes in salivary parameters, probably due to the course and the molecular characteristics of the disease, such as an impairment of salivary composition with an increased total protein concentration and a reduced salivary flow rate, sialic acid concentration,

Conflict of interest

All authors of the present manuscript declare that there is no actual or potential conflict of interest including any financial, personal or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence our work.

Acknowledgements

We are grateful to the team of the Department of Pediatrics/Pulmonology, School of Medical Sciences of Santa Casa of Sao Paulo, and for CAPES Foundation (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for the financial support.

References (40)

  • C. Johnson et al.

    Factors influencing outcomes in cystic fibrosis. A center-based analysis

    Chest

    (2003)
  • E. Kerem et al.

    Standards of care for patients with cystic fibrosis: A European consensus

    Journal of Cystic Fibrosis

    (2005)
  • S. Noël et al.

    Stimulation of salivary secretion in vivo by CFTR potentiators in Cftr+/+ and Cftr−/− mice

    Journal of Cystic Fibrosis

    (2008)
  • G.B. Proctor et al.

    Regulation of salivary gland function by autonomic nerves

    Autonomic Neuroscience

    (2007)
  • T.D. Azevedo et al.

    Presence of developmental defects of enamel in cystic fibrosis patients

    Journal of Dentistry for Children (Chicago)

    (2006)
  • J. Blomfield et al.

    Parotid gland function in children with cystic fibrosis and child control subjects

    Pediatric Research

    (1976)
  • A.M. Cantin et al.

    Plasma biomarkers and cystic fibrosis lung disease

    Clinical & Investigative Medicine

    (2012)
  • G.R. Cutting

    Cystic fibrosis genetics: from molecular understanding to clinical application

    Nature Reviews Genetics

    (2015)
  • T. Deepa et al.

    Saliva as a pontencial diagnostic tool

    Indian Journal of Medical Sciences

    (2010)
  • J.A. Dodge et al.

    CF mortality and survival in the UK: 1947–2003

    European Respiratory Journal

    (2007)
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