Periodontal disease prevalence and oral hygiene status of adults with cystic fibrosis: A case-control study.

AIM: To investigate the prevalence of gingivitis and periodontitis, and the oral hygiene status of adults with cystic fibrosis (CF) in the Republic of Ireland. MATERIALS AND METHODS: A case-control study in the form of a clinical examination of 92 adults with a diagnosis of CF was carried out in the adult CF unit in Cork University Hospital. A 40-item questionnaire was used to capture socio-demographic variables and medical and dental information. Two calibrated examiners carried out a periodontal assessment on participants, using the WHO-recommended CPI-modified index, and oral hygiene status was measured using the Greene-Vermillion index. The results were compared with a population-based control group of similar socio-demographic profile. RESULTS: Oral hygiene levels (plaque and calculus) were significantly worse in people with CF, with a median plaque index of 0.83 (interquartile range [IQR] 0.333-1.542) in the CF group compared with 0.5 (IQR 0.167-0.667) in the non-CF group. Calculus index in the CF group was 0.33 (IQR 0.17-0.83) compared with 0.33 (IQR 0.125-0.33) in the non-CF group. However, periodontal disease levels were significantly lower in the CF group. Gingivitis (bleeding on probing ≥ 10% sites) was seen in 67.4% of the CF group, compared with 83.7% of the non-CF group, OR 0.365 (95% confidence interval [CI] 0.181-0.736), relative risk (RR) 0.779 (95% CI 0.655-0.928). Mild periodontitis (periodontal probing depth [PPD] < 5 mm) was seen in 15.2% of the CF group, compared with 31.5% of the non-CF group, OR 0.390 (CI 0.190-0.800), RR 0.483 (95% CI 0.273-0.852). Severe periodontitis (PPD ≥ 6 mm) was seen in 0% of the CF group, compared with 9.8% of the non-CF group. There was a tendency, albeit non-significant, towards reduced periodontitis in PWCF who regularly took antibiotics, particularly azithromycin. CONCLUSIONS: In this study, adults with CF had poor oral hygiene practices, with high levels of plaque and calculus. Despite this finding, adults with CF had lower levels of clinical gingivitis and periodontitis than seen in a non-CF control group. Further study is required to examine the causes of this phenomenon.

The prevalence of developmental defects of enamel in people with cystic fibrosis: a systematic review.

BACKGROUND: Oral health impacts systemic health, individual well-being, and quality of life. It is important to identify conditions that may exacerbate oral disease to aid public health and policy development and promote targeted patient treatment strategies. Developmental defects can increase an individual's risk of dental caries, hypersensitivity, premature tooth wear, erosion, and poor aesthetics. As part of an ongoing study assessing oral health in adults with cystic fibrosis at Cork University Dental School and Hospital, a systematic review of available literature was conducted to assess the prevalence of enamel defects in people with cystic fibrosis. AIMS: To critically evaluate the literature to determine if the prevalence of developmental defects of enamel is higher in people with cystic fibrosis (PwCF). METHODS: Data Sources: Three online databases were searched Embase, Scopus, and Web of Science Core Collection. Studies that examined an association between cystic fibrosis and developmental defects of enamel were included in this systematic review. RESULTS: The initial search identified 116 publications from the following databases Embase, Web of Science Core Collection, and Scopus. Eleven studies were included for qualitative analysis. Nine studies concluded that PwCF had a higher prevalence of enamel defects than control people and one study found no difference in cystic fibrosis (CF) status. All studies had a risk of bias that may influence study results and their interpretation. CONCLUSIONS: The results of the systematic review show a consistent pattern that PwCF have a higher prevalence of DDE than people without CF. Genetic dysfunction, chronic systemic infections, and long-term antibiotic use are possible aetiological causes. This review highlights the need for future studies to investigate if DDEs are caused by the underlying CFTR mutation or as a consequence of disease manifestations and/or management.

In vitro assessment of CSA-131 and CSA-131 poloxamer form for the treatment of Stenotrophomonas maltophilia infections in cystic fibrosis.

BACKGROUND: Stenotrophomonas maltophilia is a Gram-negative bacterium resistant to several antibiotics and its prevalence in cystic fibrosis (CF) patients is increasing. OBJECTIVES: To evaluate the effects of ceragenins, non-peptide mimics of antimicrobial peptides, against both planktonic and biofilm forms of S. maltophilia and the cytotoxicity of ceragenins to the IB3-1 CF cell line. METHODS: Ceragenin CSA-131, with and without 5% Pluronic® F127 (a non-ionic amphiphilic poloxamer), and ceragenin CSA-13 were evaluated against S. maltophilia clinical isolates (n = 40). MICs and MBCs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1×, 2× and 4× MICs of ceragenins. The highest non-cytotoxic concentrations of ceragenins against IB3-1, a CF cell line, were determined by MTT assay. The effects of ceragenins against biofilm adhesion, formation and mature biofilms were investigated. RESULTS: CSA-131 with Pluronic® F127 displayed the lowest MICs (MIC50/MIC90: 1/2 mg/L) followed by CSA-131 (MIC50/MIC90: 2/4 mg/L), while those of CSA-13 were much higher (MIC50/MIC90: 16/32 mg/L). According to time-kill curve results, all concentrations at 4× MICs of ceragenins showed bactericidal activity (3 log reduction) after 4 h. While CSA-131 and CSA-131-poloxamer inhibited biofilm adhesion and formation by 87.74% and 83.42%, respectively, after 24 h, CSA-131 was more effective on mature biofilms. Formulating CSA-131 in poloxamer micelles did not affect the cytotoxicity of CSA-131 to IB3-1 cells. CONCLUSIONS: CSA-131 could be a potential antimicrobial agent for the treatment of S. maltophilia infections in CF, due to its low cytotoxicity on the CF cell line and good antimicrobial and antibiofilm effects.

Pharmacological and Genomic Approaches in Management of Cystic Fibrosis.

Cystic fibrosis (CF) is an inherited recessive autosomal disorder that affects the lungs, the digestive system, and secretory glands. It is a lethal condition caused by a mutation in the gene cystic-fibrosis-transmembrane-conductance- regulator (CFTR), which leads to defects in ion channels and results in obstruction of mucus in airway channels. Unbalanced ion exchange causes impaired water transport and accumulation of viscous mucus in the air way leads to bacterial colonization, for example, with Staphylococcus aureus. The most common mutation is the deletion of nucleotides in epithelial membrane; hence, it is a multiple-organ-defective disease that mostly effects the lungs. Researchers are working on gene therapy that aims to introduce a normal CFTR gene copy into the epithelial cells of lungs. Several approaches have been designed to improve transepithelial ion transport in CF patients. Normal CFTR gene delivery has been performed using viral and nonviral vectors, but these approaches are not more efficient against the cell barriers. Enzymes may be used that inhibit the sphingolipid to provide proper microenvironment for the CFTR gene product. Thymosin alpha-1 has also been reported as a potential corrector in treatment of CF.

Biofilms of Mycobacterium abscessus Complex Can Be Sensitized to Antibiotics by Disaggregation and Oxygenation.

Pulmonary infection with the multidrug-resistant Mycobacterium abscessus complex (MABSC) is difficult to treat in individuals with cystic fibrosis (CF). MABSC grows as biofilm aggregates in CF patient lungs, which are known to have anaerobic niches. How aggregation and anoxic conditions affect antibiotic tolerance is not well understood. We sought to determine whether disaggregation and oxygen availability sensitize MABSC isolates to recommended antibiotics. We tested the susceptibilities of 33 isolates from 22 CF patients with MABSC infection and a reference strain to the following antibiotics: amikacin, azithromycin, cefoxitin, ciprofloxacin, clarithromycin, imipenem, kanamycin, linezolid, moxifloxacin, rifampin, tigecycline, and sulfamethoxazole-trimethoprim. Isolates were grown in Mueller-Hinton broth with and without the disaggregating detergent Tween 80 (5%). Time-kill curves at days 1 and 3 were generated for oxic and anoxic amikacin treatment in 4-fold dilutions ranging from 2 to 512 mg liter-1 Scanning electron microscopy was used to visualize the aggregation patterns, while confocal laser scanning microscopy and microrespirometry were used to visualize biofilm growth patterns. Disruption of MABSC aggregates increased susceptibility to amikacin, tigecycline, kanamycin, azithromycin, imipenem, cefoxitin, and clarithromycin (P < 0.05, n = 29 to 31). Oxygenation enhanced the killing of disaggregated MABSC isolates by amikacin (P < 0.05) by 1 to 6 log units when 2 to 512 mg liter-1 of amikacin was used. This study explains why current drug susceptibility testing results correlate poorly with treatment outcomes. The conditions achieved by oxic culturing of planktonic isolates in vitro do not resemble the hypoxic conditions in CF patient lungs. Biofilm disruption and increased O2 availability during antibiotic therapy may be new therapeutic strategies for chronic MABSC infection.

Estimation of Proinflammatory Factors in the Saliva of Adult Patients with Cystic Fibrosis and Dental Caries.

Introduction: The available literature lacks data regarding the levels of resistin, lysozyme, lactoferrin, α-amylase activity, pH, and saliva buffer capacity, as well as oral health and hygiene in the group of adult patients with cystic fibrosis (CF). The aim of the research was to assess the selected saliva parameters in patients diagnosed with cystic fibrosis. Materials and methods: Examined group was composed of 40 patients diagnosed with CF, while the control group of 40 healthy individuals. Both groups underwent the same scheme of the assessment (DMT index, salivary pH, buffer capacity, analysis of total sialic acid, total protein estimation, lysozyme levels estimation, lactofferin levels measurement, α-amylase activity, estimation of the levels of resistin and TNF-α). Results: In the examined group, there were higher values of decayed teeth as well as values of sialic acid, total protein, lactoferrin, α-amylase, and TNF-α. However, mean lysozyme, and resistin levels, as well as pH and buffer capacity of the saliva, were lower. Conclusions: New diagnostic methods, including the evaluation of selected salivary biochemical parameters, may indicate the existence of factors predisposing to severe tooth decay in the study group. Appropriate preventive treatment to combat dental caries in adult patients with CF will significantly improve their comfort and life expectancy.

Secretory IgA-mediated immune response in saliva and early detection of Pseudomonas aeruginosa in the lower airways of pediatric cystic fibrosis patients.

Pseudomonas aeruginosa (Pa) detection in the paranasal sinuses may help to prevent or postpone bacterial aspiration to the lower airways (LAW) and chronic lung infection in cystic fibrosis (CF). We assessed the ability of an ELISA test for measurement of specific Pa secretory IgA (sIgA) in saliva (a potential marker of sinus colonization) to early detect changes in the Pa LAW status (indicated by microbiological sputum or cough swab culture and specific serum IgG levels) of 65 patients for three years, in different investigation scenarios. Increased sIgA levels were detected in saliva up to 22 months before changes in culture/serology. Patients who remained Pa-positive had significantly increased sIgA levels than patients who remained Pa-negative, both at the baseline (39.6 U/mL vs. 19.2 U/mL; p = 0.02) and at the end of the follow-up (119.4 U/mL vs. 25.2 U/mL; p < 0.001). No association was found between sIgA levels in saliva and emergence or recurrence of Pa in the LAW. A positive median sIgA result in the first year of follow-up implied up to 12.5-fold increased risk of subsequent Pa exposure in the LAW. Our test detected early changes in the P. aeruginosa LAW status and risk of exposure to P. aeruginosa in the LAW with two years in advance. Comparison with sinus culture is needed to assess the test's ability to identify CF patients in need of a sinus approach for Pa investigation, which could provide opportunities of Pa eradication before its aspiration to the lungs.

Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis.

BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation and by temporarily increasing functional residual capacity. The developers of the PEP technique recommend using PEP with a mask in order to avoid air leaks via the upper airways and mouth. In addition, increasing forced residual capacity (FRC) has not been demonstrated using mouthpiece PEP. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect. This is an update of a previously published review. OBJECTIVES: To determine the effectiveness and acceptability of PEP devices compared to other forms of physiotherapy as a means of improving mucus clearance and other outcomes in people with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2017. Most recent search of the Group's CF Trials Register: 20 February 2019. SELECTION CRITERIA: Randomised controlled studies in which PEP was compared with any other form of physiotherapy in people with CF. This included, postural drainage and percussion (PDPV), active cycle of breathing techniques (ACBT), oscillating PEP devices, thoracic oscillating devices, bilevel positive airway pressure (BiPaP) and exercise. DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion and exclusion criteria to publications, assessed the risk of bias of the included studies and assessed the quality of the evidence using the GRADE recommendations. MAIN RESULTS: A total of 28 studies (involving 788 children and adults) were included in the review; 18 studies involving 296 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform any meta-analysis. In 22 of the 28 studies the PEP technique was performed using a mask, in three of the studies a mouthpiece was used with nose clips and in three studies it was unclear whether a mask or mouthpiece was used. These studies compared PEP to ACBT, autogenic drainage (AD), oral oscillating PEP devices, high-frequency chest wall oscillation (HFCWO) and BiPaP and exercise. Forced expiratory volume in one second was the review's primary outcome and the most frequently reported outcome in the studies (24 studies, 716 participants). Single interventions or series of treatments that continued for up to three months demonstrated little or no difference in effect between PEP and other methods of airway clearance on this outcome (low- to moderate-quality evidence). However, long-term studies had equivocal or conflicting results regarding the effect on this outcome (low- to moderate-quality evidence). A second primary outcome was the number of respiratory exacerbations. There was a lower exacerbation rate in participants using PEP compared to other techniques when used with a mask for at least one year (five studies, 232 participants; moderate- to high-quality evidence). In one of the included studies which used PEP with a mouthpiece, it was reported (personal communication) that there was no difference in the number of respiratory exacerbations (66 participants, low-quality evidence). Participant preference was reported in 10 studies; and in all studies with an intervention period of at least one month, this was in favour of PEP. The results for the remaining outcome measures (including our third primary outcome of mucus clearance) were not examined or reported in sufficient detail to provide any high-quality evidence; only very low- to moderate-quality evidence was available for other outcomes. There was limited evidence reported on adverse events; these were measured in five studies, two of which found no events. In a study where infants performing either PEP or PDPV experienced some gastro-oesophageal reflux , this was more severe in the PDPV group (26 infants, low-quality evidence). In PEP versus oscillating PEP, adverse events were only reported in the flutter group (five participants complained of dizziness, which improved after further instructions on device use was provided) (22 participants, low-quality evidence). In PEP versus HFCWO, from one long-term high-quality study (107 participants) there was little or no difference in terms of number of adverse events; however, those in the PEP group had fewer adverse events related to the lower airways when compared to HFCWO (high-certainty evidence). Many studies had a risk of bias as they did not report how the randomisation sequence was either generated or concealed. Most studies reported the number of dropouts and also reported on all planned outcome measures. AUTHORS' CONCLUSIONS: The evidence provided by this review is of variable quality, but suggests that all techniques and devices described may have a place in the clinical treatment of people with CF. Following meta-analyses of the effects of PEP versus other airway clearance techniques on lung function and patient preference, this Cochrane Review demonstrated that there was high-quality evidence that showed a significant reduction in pulmonary exacerbations when PEP using a mask was compared with HFCWO. It is important to note that airway clearance techniques should be individualised throughout life according to developmental stages, patient preferences, pulmonary symptoms and lung function. This also applies as conditions vary between baseline function and pulmonary exacerbations.

Aerosolized Bovine Lactoferrin Counteracts Infection, Inflammation and Iron Dysbalance in A Cystic Fibrosis Mouse Model of Pseudomonas aeruginosa Chronic Lung Infection.

Cystic fibrosis (CF) is a genetic disorder affecting several organs including airways. Bacterial infection, inflammation and iron dysbalance play a major role in the chronicity and severity of the lung pathology. The aim of this study was to investigate the effect of lactoferrin (Lf), a multifunctional iron-chelating glycoprotein of innate immunity, in a CF murine model of Pseudomonas aeruginosa chronic lung infection. To induce chronic lung infection, C57BL/6 mice, either cystic fibrosis transmembrane conductance regulator (CFTR)-deficient (Cftrtm1UNCTgN(FABPCFTR)#Jaw) or wild-type (WT), were intra-tracheally inoculated with multidrug-resistant MDR-RP73 P. aeruginosa embedded in agar beads. Treatments with aerosolized bovine Lf (bLf) or saline were started five minutes after infection and repeated daily for six days. Our results demonstrated that aerosolized bLf was effective in significantly reducing both pulmonary bacterial load and infiltrated leukocytes in infected CF mice. Furthermore, for the first time, we showed that bLf reduced pulmonary iron overload, in both WT and CF mice. In particular, at molecular level, a significant decrease of both the iron exporter ferroportin and iron storage ferritin, as well as luminal iron content was observed. Overall, bLf acts as a potent multi-targeting agent able to break the vicious cycle induced by P. aeruginosa, inflammation and iron dysbalance, thus mitigating the severity of CF-related pathology and sequelae.

ANALYSIS OF LOCAL IMMUNITY INDICATORS OF THE ORAL CAVITY AND DEGREE OF GINGIVITIS DEPENDING ON MUTATION OF CFTR GENE IN CHILDREN WITH CYSTIC FIBROSIS.

The aim of the work was to establish the relationship between the genotype of the cystic fibrosis transmembrane conductance regulator (CFTR), the level of local immune reactivity and the degree of chronic gingivitis in children with cystic fibrosis. The study has shown significant differences in the local immunity indices of the oral mucosa and the condition of periodontal tissues in children with cystic fibrosis in comparison with the control group. The features of the course of dental pathology among sick children, depending on the type of CFTR gene mutation are determined. Disturbance of mucosal immunity of the oral cavity in children with cystic fibrosis is manifested by a decrease in lysozyme activity in mixed saliva by 1.5 times and level of secretory immunoglobulins IgA by 1.4 times. A consequence of this is an increase of the degree of dysbiosis of the oral cavity by 3.7 times. At the same time, a lesser imbalance in the microflora and lysozyme activity observed in the homozygote group of the F508del mutation, and heterozygotes of the F508del mutation have the most severe manifestations of chronic gingivitis.

Are children and adolescents with cystic fibrosis at lower risk of caries?

DATA SOURCES: The Medline, Embase and Web of Science databases were searched. STUDY SELECTION: Human clinical trials, evaluation studies and systematic reviews related to dental caries prevalence in children and adolescents with CF under age 18 years were included. DATA EXTRACTION AND SYNTHESIS: Standard date items were extracted and risk of bias was assessed using adapted criteria from the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. A qualitative synthesis was conducted. RESULTS: Fifteen studies met the inclusion criteria, 12 studies were considered as being at high risk of bias and three as medium risk. Ten studies concluded that children with CF had significantly lower caries prevalence than control children, while three studies reported that children with CF had higher caries prevalence, and two studies found no difference by CF status. All of the studies had limitations that may bias the results. CONCLUSIONS: While children with CF may be at lower risk for dental caries, adolescents with CF may not be at lower caries than those without CF. Additional research is needed to evaluate a potentially flawed paradigm regarding caries risk in children and adolescents with CF.

The association between cystic fibrosis-related diabetes and periodontitis in adults: A pilot cross-sectional study.

OBJECTIVES: Periodontitis is a highly prevalent complication of diabetes. However, the association between cystic fibrosis-related diabetes (CFRD) and periodontitis has not yet been evaluated. The objective of this study was to assess if: 1) CFRD is associated with periodontitis among adults with CF, and 2) periodontitis prevalence differs by CF and diabetes status. METHODS: This was a pilot cross-sectional study of the association between CFRD and periodontitis in adults with cystic fibrosis (CF) (N = 32). Historical non-CF controls (N = 57) from the U.S. National Health and Nutrition Examination Survey (NHANES) dataset were frequency matched to participants with CF on age, sex, diabetes status, and insulin use. We defined periodontitis using the U.S. Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition, as the presence of two or more interproximal sites with CAL ≥3 mm and two or more interproximal sites with PD ≥4 mm (not on the same tooth) or one site with PD ≥5 mm. Because NHANES periodontal data were only available for adults ages ≥30 years, our analysis that included non-CF controls focused on this age group (CF N = 19, non-CF N = 57). Based on CF and diabetes status, we formed four groups: CFRD, CF and no diabetes, non-CF with diabetes, and non-CF and no diabetes (healthy). We used the Fisher's exact test for hypotheses testing. RESULTS: There was no association between CFRD and periodontitis for participants with CF ages 22-63 years (CFRD 67% vs. CF no diabetes 53%, P = 0.49), this was also true for those ages ≥30 years (CFRD 78% vs. CF no diabetes 60%, P = 0.63). For the two CF groups, the prevalence of periodontitis was significantly higher than for healthy controls (CFRD 78% vs. healthy 7%, P<0.001; CF no diabetes 60% vs. healthy 7%, P = 0.001) and not significantly different than the prevalence for non-CF controls with diabetes (CFRD 78% vs. non-CF with diabetes 56%, P = 0.43; CF no diabetes 60% vs. non-CF with diabetes 56%, P = 0.99). CONCLUSION: Among participants with CF, CFRD was not associated with periodontitis. However, regardless of diabetes status, participants with CF had increased prevalence of periodontitis compared to healthy controls.

The prevalence of developmental defects of enamel in a cohort of adults with cystic fibrosis - A cross sectional study.

OBJECTIVES: Cystic Fibrosis is an autosomal recessive condition. It is a multisystem disease treated with a broad range of pharmacological therapies, diet and nutrition, and physiotherapy. Previous studies suggest that people with cystic fibrosis have a higher prevalence of developmental defects of enamel which may place this population at a greater risk of developing oral diseases such as caries. The aim of this study was to assess a cohort of people with cystic fibrosis (PwCF) for the presence of developmental defects of enamel and compare the results with a control group of people without cystic fibrosis. METHODS: A cross sectional study involving 92 participants with cystic fibrosis and 92 controls was conducted in Cork University Dental School & Hospital. All participants completed a detailed questionnaire prior to undergoing a full clinical examination. The Developmental Defect of Enamel Index was used as a measurement index. All data was statistically analysed with the help of statisticians from Cystic Fibrosis Registry of Ireland. RESULTS: 64 % (n = 59) of PwCF had enamel defects compared to just 30 % (n = 28) of people without cystic fibrosis. The median number of teeth affected by enamel defects in the study group was 1.5, compared to 0 in the control group. CONCLUSION: In this study the cohort of PwCF had more enamel defects than people without CF. Further research is required to investigate the aetiology of these findings. CLINICAL SIGNIFICANCE: Clinicians should be vigilant after teeth have erupted in PwCF as they may have an increased susceptibility to developmental defects of enamel.

Inhaled antibiotics: A promising drug delivery strategies for efficient treatment of lower respiratory tract infections (LRTIs) associated with antibiotic resistant biofilm-dwelling and intracellular bacterial pathogens.

Antibiotic-resistant bacteria associated with LRTIs are frequently associated with inefficient treatment outcomes. Antibiotic-resistant Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, and Staphylococcus aureus, infections are strongly associated with pulmonary exacerbations and require frequent hospital admissions, usually following failed management in the community. These bacteria are difficult to treat as they demonstrate multiple adaptational mechanisms including biofilm formation to resist antibiotic threats. Currently, many patients with the genetic disease cystic fibrosis (CF), non-CF bronchiectasis (NCFB) and chronic obstructive pulmonary disease (COPD) experience exacerbations of their lung disease and require high doses of systemically administered antibiotics to achieve meaningful clinical effects, but even with high systemic doses penetration of antibiotic into the site of infection within the lung is suboptimal. Pulmonary drug delivery technology that reliably deliver antibacterials directly into the infected cells of the lungs and penetrate bacterial biofilms to provide therapeutic doses with a greatly reduced risk of systemic adverse effects. Inhaled liposomal-packaged antibiotic with biofilm-dissolving drugs offer the opportunity for targeted, and highly effective antibacterial therapeutics in the lungs. Although the challenges with development of some inhaled antibiotics and their clinicals trials have been studied; however, only few inhaled products are available on market. This review addresses the current treatment challenges of antibiotic-resistant bacteria in the lung with some clinical outcomes and provides future directions with innovative ideas on new inhaled formulations and delivery technology that promise enhanced killing of antibiotic-resistant biofilm-dwelling bacteria.

Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection.

RATIONALE: Arikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition. OBJECTIVES: To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa. METHODS: 105 subjects were evaluated in double-blind, placebo-controlled studies. Subjects were randomised to once-daily Arikace (70, 140, 280 and 560 mg; n=7, 5, 21 and 36 subjects) or placebo (n=36) for 28 days. Primary outcomes included safety and tolerability. Secondary outcomes included lung function (forced expiratory volume at one second (FEV1)), P aeruginosa density in sputum, and the Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R). RESULTS: The adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV1 was higher in the 560 mg dose group at day 28 (p=0.033) and at day 56 (28 days post-treatment, 0.093L±0.203 vs -0.032L±0.119; p=0.003) versus placebo. Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021). The Respiratory Domain of the CFQ-R increased by the Minimal Clinically Important Difference (MCID) in 67% of Arikace subjects (560 mg) versus 36% of placebo (p=0.006), and correlated with FEV1 improvements at days 14, 28 and 42 (p<0.05). An open-label extension (560 mg Arikace) for 28 days followed by 56 days off over six cycles confirmed durable improvements in lung function and sputum P aeruginosa density (n=49). CONCLUSIONS: Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection.

Dental caries prevalence in children and adolescents with cystic fibrosis: a qualitative systematic review and recommendations for future research.

BACKGROUND: Children and adolescents with cystic fibrosis (CF) are believed to be at low risk for dental caries, but this paradigm has not been critically evaluated. AIMS: To conduct a qualitative systematic review of the international literature on dental caries prevalence in children and adolescents with CF and make recommendations on future CF-related oral health research priorities. DESIGN: The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was used to identify relevant studies published between 1960 and 2013. RESULTS: The search resulted in 696 studies. Fifteen publications were included in the qualitative systematic review. Ten studies concluded that children with CF had significantly lower caries prevalence than control children, three studies reported that children with CF had higher caries prevalence, and two studies found no difference by CF status. Of the seven studies including age-based subgroup analyses, only one study supported the current paradigm. All studies had limitations that may bias study results. CONCLUSIONS: While children with CF may be a lower risk for dental caries, adolescents with CF may not be at lower caries than those without CF. Additional research is needed to evaluate a potentially flawed paradigm regarding caries risk in children and adolescents with CF.

Oral health and cystic fibrosis in pediatrics: A survey of health professionals.

BACKGROUND: Children with cystic fibrosis (CF) are usually managed by hospital-based, multidisciplinary teams (MDTs). This study aimed to investigate oral health perspectives, training, and practices of health professionals working with children with CF. METHODS: Data were collected through an online survey distributed to health professionals caring for children with CF by the CF Director in 12 Australian hospitals. The questions related to perspectives, training, and dental referral/advice relating to oral health for children with CF. The data were analyzed using descriptive statistics. RESULTS: Forty-four participants (26 physicians, 8 nurses, 6 physiotherapists, 2 dieticians, 1 psychologist, and 1 pharmacist) completed the survey. Most (n = 33, 75%) indicated they rarely/never check or discuss dental health. Of those who did, most reported lacking skills to inspect teeth and discuss dental health. Frequently reported barriers were lack of skills, training, knowledge, and time. Most respondents (n = 30, 68%) indicated they rarely/never recommend patients to see the dentist. The most frequently reported barrier to referrals was not considering it part of their role (43%). CONCLUSIONS: Closer working relations between CF units and dental teams may remove barriers that prevent non-dental clinicians from supporting patients with CF maintain oral health. Better integration of dental care within the MDT through improved professional training, increased referral practices, and availability of digital resources may help to improve dental care for all children, including children and adolescents with CF.

Periodontitis Risk Factors in Adults with Cystic Fibrosis: A pilot study.

Purpose Individuals with cystic fibrosis (CF) present with multiple condition-specific risk factors for periodontitis including CF-related diabetes, chronic inhaled treatments that induce xerostomia, and increased systemic inflammation because of frequent lung infections. General factors like age, oral hygiene, and diet may also contribute to the risk of periodontitis. However the relative importance of these specific risk factors and periodontitis in individuals with CF has not yet been evaluated. The purpose of this pilot study was to assess the associations between CF condition-specific and general risk factors and the prevalence of periodontitis in adults with CF.Methods This cross-sectional pilot study was designed to assess a multifactorial model of periodontitis risk factors in a population in adults with CF who were recruited from the University of Washington Adult CF center. Periodontitis was defined using the Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) case definition. Risk factors included condition-specific and general factors. Differences between participants with moderate/severe periodontitis and those with no/mild periodontitis was assessed using the Mann-Whitney test, the Fisher's exact test, and the exact chi-square test (α=0.05).Results Thirty-two participants were enrolled. Twenty-eight percent of the participants had moderate periodontitis, 72% had no/mild periodontitis; none of the participants had severe periodontitis. There were no significant differences in condition-specific factors between between the two study groups. Participants with moderate periodontitis were older (p=0.028) and reported daily flossing in higher proportions than those with no/mild periodontitis (p=0.023).Conclusions The findings from this pilot study suggest that future research is needed to determine whether sociodemographic and other general risk factors are more important contributors to periodontitis risk than CF-specific factors.

Adolescent Patient with Cystic Fibrosis Presents with Suspected Ludwig Angina.

A 15-year-old boy attended Emergency Department with a complaint of difficulty in breathing due to dental infection. A pulmonologist was consulted regarding the severity of the cystic fibrosis. The patient was admitted and intravenous (IV) fluids and antibiotics were given. The infected mandibular right first permanent molar tooth # 30 was extracted under IV ketamine dissociative anesthesia in the hospital setting.