To install StudyMoose App tap and then “Add to Home Screen”
Save to my list
Remove from my list
Cystic Fibrosis is a genetic disease that is caused by a mutation in the CFTR gene. This disease can have an impact on many organ systems however its biggest insult might be on the pulmonary system. In this population it has been found that treatment with inhaled hypertonic saline, it has also been shown that 20% of CF patients cannot tolerate treatment using Hypertonic Saline.
The goal of this study is to determine if adding Hyaluronic Acid to the inhaled Hypertonic Saline improves the tolerability allowing which would allow more of this population to receive this beneficial treatment.
Methods: Relevant published studies were obtained using Medline by searching “Cystic Fibrosis”, “hyaluronic Acid”, “hyaluronic acid and Cystic Fibrosis”, “hypertonic Saline”, “Inhaled hypertonic saline”, Hypertonic Saline and hyaluronic acid”.
There was no time limit established however all data used is within the last ten years. Only studies published in credible medical journals were considered.
Results: The results of these studies conclude that Hyaluronic Acid has a role in the treatment of CF as well as other chronic pulmonary infections as an adjuvant therapy to reduce the symptoms that limit the use of hypertonic saline therapy.
Verified writer
Proficient in: Biology
5 (876)
“ Have been using her for a while and please believe when I tell you, she never fail. Thanks Writer Lyla you are indeed awesome ”
The symptoms that were shown to be reduced include cough, throat irritation, salty taste and bronchospasm.
Cystic fibrosis is a genetic disease that primarily effects the respiratory system, leading to increased amounts of respiratory tract infections. The disease is caused by a defective gene that causes defective airway ion transport resulting in less airway surface liquid, in other words the airway is dehydrated.
Less airway surface liquid leads to the production of a sticky and thick mucus in the lungs. This mucus clogs the airways leading to lung damage that causes entire respiratory system failure. The progression of CF is defined by the frequency of exacerbations, which are acutely worsening pulmonary symptoms, including reduced spirometry, increased sputum production, dyspnea all of which can be reversible. Exacerbation frequency can be used to predict patient mortality. An effort to reduce the amount of exacerbations and pro-long the time between the exacerbation is shown to slow the long-term decline in pulmonary function in patients with CF.
Hypertonic Saline in a nebulized form has been shown to improve the hydration status of the airways. Inhaled hypertonic saline osmotically draws water into the airway which improves mucus clearance by thinning the mucus, thereby improving pulmonary function and reducing the incidence of acute exacerbation in CF patients.
In addition to the inability to clear the thick mucus, characteristic of CF, is abundance of bacteria in the respiratory tract. In multiple trials comparing the efficacy of nebulized treatments for CF and other chronic pulmonary diseases, Hypertonic saline was found to be harsh on the respiratory tract and intolerable in many instances. Roughly 20% of patients cannot tolerate the use of Hypertonic Saline in their treatment regimen. Intolerances were typically identified as symptoms including cough, pharyngeal irritation, bronchospasm, and salty taste. This review will explore the effectiveness of hyaluronic acid as an adjuvant therapy to improve the tolerability of nebulized hypertonic saline in the CF population. Hyaluronic Acid is substance that is naturally present in our body’s tissues.
Hyaluronic acid has many uses in medicine, currently it is approved in treatment of osteoarthritis, certain plastic surgeries as well as optic surgeries. Due to the nature of this substance it is a natural lubricant, it contains 1000-fold more water than polymer. It is said that one of the major roles of Hyaluronic Acid is the regulation of fluid balance due to its high water binding capacity.
Four publications which explored the use of hyaluronic acid as an adjuvant therapy to increase the tolerability of nebulized Cystic Fibrosis treatments are included in this review. Three of the articles focus on the use of hyaluronic acid to increase the tolerability of inhaled hypertonic saline specifically as it pertains to the CF population. The other looks at hyaluronic acid to improve the tolerability of nebulized Hypertonic Saline in bronchiectasis patients.
Buonpensiero et al. used a randomized crossover trial, comparing the use of nebulized hypertonic saline and the use of nebulized hypertonic saline with the addition of hyaluronic acid, to test the hypothesis that adding hyaluronic acid to the hypertonic saline breathing treatments significantly improves the tolerability of the therapy, specifically regarding the presence or absence of cough during and immediately after treatment. The primary outcome was the tolerability of the inhaled solution due to cough.
Additionally, the tolerability was assessed regarding other attributes they deemed to contribute to the tolerability of the treatment including throat irritation, salty taste, and the perceived pleasantness of the inhalation. The trial included 20 participants of the 190 patients approached to be involved in the study. Inclusion criteria for the study were as follows: an established diagnosis of CF, age at least 6 years, a forced expiratory volume in 1 second (FEV1) of 50% or more of the predicted value, and clinically stable lung. Exclusion criteria were evidence of reactive airways or a clinical diagnosis of asthma. Each of the participants were confirmed as having cystic fibrosis by sweat testing. The 20 participants were split into two groups of ten. To avoid selection bias a crossover design was used.
On day 1 one group would receive 5 ml of 7% hypertonic saline while the other would receive 5 ml of hypertonic saline with 0.1% hyaluronic acid added. Immediately after each inhaled dose patients rated the severity of their symptoms including cough, irritation, and saltiness. Using McNemar’s exact chi-square test with a 95% confidence interval results were scored by a four-point ordinal scale where 0 = absent and 3 = severe. Pleasantness was evaluated using a standardized five-level, Likert-type scale where 1 = very unpleasant and 5 = very pleasant. Before and after each saline inhalation participants performed standardized spirometry to evaluate the FEV1. The inhaled solution of 0.1% hyaluronic acid plus hypertonic saline significantly improved tolerability and pleasantness compared to hypertonic saline alone, and reduce adverse effects especially cough, throat irritation and salty taste. There was no significant difference in FEV1 between the two groups.
Ros et al used a randomized, double-blind, controlled clinical trial to demonstrate that the addition of hyaluronic acid to the nebulized hypertonic saline treatments in CF patients who have already shown to be intolerance to inhaled hypertonic saline improves the tolerability of the therapy. Primary endpoints of this trial include presence or absence of cough, saltiness, throat irritation and overall acceptability. Secondary endpoints of this trial look at FEV1 following the 28day treatment course. From Dec 2009-July 2011 40 patients were enrolled into the study.
Inclusion criteria were: > 8 years old with a confirmed diagnosis of CF, recruited from four Italian CF centers, clinically and therapeutically stable disease during the previous 30 days; FEV1 ‡ 50% of predicted value; previously established intolerance (cough, throat irritation, saltiness) to Hypertonic Saline solution. Exclusion criteria were: decrease in FEV1 of > 15% after Hypertonic Saline; infection with Bulkholderia cepacia; infective exacerbation requiring antibiotic treatment in the previous 15 days; noncompliance to standard therapy; having received lung transplantation; being unable to perform reproducible spirometry; being intolerant to b2 bronchodilators; being enrolled in other clinical trials.
The forty pts were randomly assigned to Two groups of 20 pts. One group received 5 ml of 7% hypertonic saline while the other would receive 5 ml of hypertonic saline with 0.1% hyaluronic acid added twice a day for 28 days. The patients received the first and last doses in the hospital, between doses were self-administered. Of the 40 to start the trial 5 pts failed to complete the trial. 2 patients from both groups dropped out due to intolerability of the therapy. One patient from the hypertonic saline only group had to drop out early due to an acute exacerbation of his disease. Patients were given recording materials and asked to record their results weekly. Using a four level likert-type scale (absent, mild, moderate, severe) results were assessed. The Wilcoxon rank sum test and the Cochran-Mantel- Haenszel test corrected for time were applied to analyze cough, throat irritation, saltiness, and final judgment. The statistical threshold was set at 0.05 for a two-tail test.
In the group receiving only hypertonic saline moderate to severe symptoms were recorded for cough 60% of the time, throat irritation 40% of the time, and saltiness 60% of the time as compared to 10%, 15% and 10% respectively in the group receiving the hyaluronic acid in addition to the hypertonic saline. Over the 28-day course of treatment there was no significant difference in the FEV1 between the two groups.
Furnari et al used single-center, prospective, randomized, double-blind, parallel-group, controlled study to test the efficacy of adding 0.1% hyaluronic acid to 5 mL of 7% hypertonic saline to improve the pleasantness and tolerability of inhaled therapy in cystic fibrosis patients. The primary goal of this study was to assess the tolerability of the inhaled therapy versus hypertonic saline alone. Another focus of the study was to test the effects of adding hyaluronic acid to hypertonic saline and the incidence of bronchospasm as Hypertonic Saline is known to cause bronchospasm in some patients. This study included 30 patients initially of which three were excluded from the final numbers.
One patient from each group failed to return the journal and one additional patient from the hypertonic saline alone group dropped out at baseline due to intolerability of the therapy. The inclusion criteria were male and female patients aged at least 10 years, diagnosed with CF, with FEV1 at least 40% of predicted value, undergoing stable antibiotic, mucolytic or anti-inflammatory treatment in the 3 months prior to study inclusion and having provided informed consent. Patients were excluded from the study if they presented any of the following: Burkholderia cepacia infection; used Hypertonic Saline therapy in the 15 days preceding enrolment; an exacerbation of infection in the 15 days preceding inclusion and which required antibiotic therapy; changes in chronic therapy (antibiotic, DNase, anti-inflammatory drugs) in the 28 days preceding enrolment.
Patients received the first and last dose on nebulized therapy in the hospital and FEV1 was recorded at baseline, one hour after initial therapy and again after the treatment regimen finished. Patients were asked to fill out a journal on days 7, 14, 21, and 28 assessing symptoms of cough, thoracic constriction, throat irritation and saltiness, and also express a pleasantness judgment on the assigned treatment. Each item was assessed using a four-point ordinal score: 1 = absent; 2 = light; 3 = moderate, and 4 = severe. The measure of pleasantness was scored using a scale from 0 to 5: 0 = disgusting and 5 = neutral. The need for β2 bronchodilators was also to be recorded daily.
The Wilcoxon rank sum test and the Cochran- Mantel-Haenszel test corrected for time were applied to analyze cough, irritation, thoracic constriction, saltiness, and final judgment. FEV1 values and β2 bronchodilator consumption were analyzed using Student’s t test. β2 bronchodilator consumption during the 4 weeks of treatment was also analyzed by analysis of variance for repeated measures. Over the course of the therapy 85.7% of the patients in the group receiving the hyaluronic acid in addition to the hypertonic saline reported no use of additional B2 bronchodilators as compared to 64.3% of the group receiving the hypertonic saline alone.
By the end of the 4 week study 78% of the patients receiving the inhaled therapy containing the hyaluronic acid reported no cough as compared to only 23% of the patients receiving hypertonic saline alone, similar results were found in regards to the other symptoms, throat irritation, constriction and saltiness were all reported at higher rates in the group that received hypertonic saline alone. This study found no difference in adverse events between the two groups.
Maiz et al used a prospective, observational, open-label study to test the hypothesis that adding 0.1% Hyaluronic acid to 5ml of 7% hypertonic saline improves the tolerance of nebulized hypertonic saline treatments in bronchiectasis patients that initially cannot tolerate hypertonic saline therapy. The primary endpoint of this study was to determine what percentage of patients identified as intolerant to hypertonic saline alone can tolerate a solution containing hyaluronic acid and hypertonic saline. Tolerance was determined based on symptomology, symptoms included cough, pharyngeal irritation, salty taste, chest tightness, dyspnea, wheezing, and nausea. This study determined that a sample size of 139 patients would be sufficient to test their hypothesis using a Clopper-Pearson formula to calculate N.
Patients were recruited for this study from November 2015- May 2017 from public teaching hospitals throughout Spain. Inclusion criteria were: >18 years old; previous diagnosis of bronchiectasis; decision of the physician to start treatment with inhaled Hypertonic Saline solution; sputum production > 30 ml every 24 hr; mean FEV1 postbronchodilator ⩾35% or ⩾1 L. Exclusion criteria were: exacerbations in the 4 weeks prior to study; treatment with oral antibiotics or systemic corticoids during the 4 weeks previous to inclusion in the study; previous hemoptysis; current treatment with inhaled Hypertonic Saline; diagnosis of aspergillosis or cystic fibrosis; pregnant women; patients enrolled in other clinical studies; or patients with treated but uncontrolled arterial hypertension.
This study included a total of 137 patients of which 92 were capable to tolerate hypertonic saline alone so they continued a 4-week course of inhaled hypertonic saline. 80 of the 92 patients were able to complete the 4-week therapy and were deemed tolerant. Of the 45 that were unable to tolerate Hypertonic Saline initially 31 were able to tolerate the solution of Hyaluronic Acid and Hypertonic Saline. 26 of the 31 were able to complete the 4-week trial and were deemed tolerant of Hypertonic Saline when Hyaluronic Acid was added. Tolerability was assessed by three parameters; 1st using a Likert-type questionnaire on symptomology; 2nd post-treatment FEV1 decrease ⩾15%; 3RD As judged by the physician administering the test.
Results of this study showed that roughly 70% of the patients that were deemed intolerant to Hypertonic Saline alone were tolerant to a solution of Hypertonic Saline and Hyaluronic Acid and roughly 84% of those patients were able to continue therapy for an extended time. The study also showed that the patients who were deemed intolerant to Hypertonic Saline initially had lower baseline pulmonary function with FEV1 of 68% of predicted versus 80% of predicted in the patients who were able to tolerate Hypertonic Saline. There was no significant difference in adverse events between the two groups.
The main findings concerning the efficacy of adding Hyaluronic Acid to Hypertonic Saline solution to improve tolerability of inhaled Hypertonic Saline therapy in the CF population support the hypothesis that adding Hyaluronic Acid to Hypertonic Saline improves the tolerability. Overall this review shows that for those patients who cannot tolerate inhaled Hypertonic Saline, due to symptoms of cough, pharyngeal irritation, bronchospasm and salty taste, Hyaluronic Acid as an adjuvant therapy should be considered. The studies used for this review all explored the same hypothesis that adding Hyaluronic Acid to Hypertonic Saline improves tolerability.
The studies appear to build upon the research of the others as opposed to contradicting the information gained by the previous study. For this reason, there is still more opportunity to research this hypothesis possibly focusing on the adverse events. Additionally, the latest research showed that the patients who typically cannot tolerate Hypertonic Saline alone have a lower baseline pulmonary function, this is perhaps another area for further research.
If it can be shown that using Hyaluronic Acid as a adjuvant to inhaled Hypertonic Saline allows those who already have lower levels of pulmonary function to adhere to a therapy that has been shown to improve long term pulmonary function by reducing the number of exacerbations, this needs further research as it can have a great impact on those patients with chronic lung disease. Another possible area of further research would be to look into different formulations of Hyaluronic Acid and Hypertonic Saline in this population as the only research available is for a very specific 0.1% Hyaluronic Acid in 5 mL of Hypertonic Saline.
Limitations of the studies used in this review include a seemingly limited sample size. The findings of the trials should be applied to a larger sample to ensure that they hold true. Another limitation of this review is that there has been very little research completed on the effects of adding Hyaluronic Acid to inhaled Hypertonic Saline. Additionally, the studies completed seem to build on the previous research without looking for evidence to contradict claims.
Research available suggests that cystic fibrosis patients unable to tolerate inhaled Hypertonic Saline would benefit from using inhaled solution containing 0.1% hyaluronic acid in 5 mL of Hypertonic Saline as a treatment to improve long term pulmonary function and reduce the frequency of exacerbations. The results of these studies conclude that Hyaluronic Acid has a role in the treatment of CF as well as other chronic pulmonary infections as an adjuvant therapy to reduce the symptoms that limit the use of hypertonic saline therapy.
The symptoms that were shown to be reduced include cough, throat irritation, salty taste and bronchospasm. Being that Hypertonic Saline has been shown to reduce the number of exacerbations and improve the long-term pulmonary function of these chronically ill patients improving the tolerance of hypertonic saline using Hyaluronic Acid can help those patients.
Improving Nebulized Hypertonic Saline Tolerance in Cystic Fibrosis with Hyaluronic Acid. (2024, Feb 16). Retrieved from https://studymoose.com/document/improving-nebulized-hypertonic-saline-tolerance-in-cystic-fibrosis-with-hyaluronic-acid
👋 Hi! I’m your smart assistant Amy!
Don’t know where to start? Type your requirements and I’ll connect you to an academic expert within 3 minutes.
get help with your assignment
