The Effect of Orally Administered Gelatin on Symptom Resolution in Chronic Persistent Cough: A Randomized Clinical Trial Study

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Article Information:


Group: 2009
Subgroup: Volume 11, Issue 2
Date: April 2009
Type: Original Article
Start Page: 145
End Page: 148

Authors:

  • Ali Asghar Zolghadrasli
  • Assistant Professor at Islamic Azad University, Estahban, Fars, Iran
  • AA Zolghadrasli
  • Student Research Center, Shiraz University of Medical Sciences, Shiraz, Fars, Iran

      Correspondence:

      Affiliation: Assistant Professor at Islamic Azad University
      City, Province: Estahban, Fars
      Country: Iran
      Tel: +98-917-3157833
      Fax:
      E-mail: azolghadr@sums.ac.ir

Abstract:


Background: The term chronic cough signifies the cough lasting for more than three weeks and is associated with different morbidities. Despite its importance, the management is often unsatisfactory. Gelatin is widely used in Iranian traditional medicine for chronic cough.  This study aims to test gelatin as a possible therapy for chronic cough.

 

Methods: One hundred patients with chronic cough without any other co-morbidities were randomly divided into two groups. The first group continued their previous antitussive medication and the second group received gelatin for 3-5 days.

 

Results: In first group, 52% were female and 48% male (42.9±12.8 years) while these figures for the 2nd group, were 46% and 54% (41.4±14.7). Cough duration in the first group was 6.4 weeks and 6.4 weeks in the second group. In the first group, 16% reported no response to the therapy, 30% poor response, 28% fair response, 18% good response, and 8% excellent response respectively. In the second group, the figures were 4%, 20%, 32%, 38% and 6% respectively.

 

Conclusion: Although the number of participants was not large enough to determine a statistical significance, it seems that gelatin had relieved the patients of their cough more than common antitussive medications. This study can provide the ground for further studies, especially clinical trials to evaluate the efficacy of gelatin for the treatment of chronic persistent cough.

Keywords: Oral; Gelatin; Symptom; Treatment; Chronic persistent cough

Manuscript Body:


Introduction

 

Cough is the most common presenting complaint in adults seeking medical treatment in an ambulatory setting and is one of the top 5 reasons for which medical attention is sought.1,2 When it lasts for more than three weeks, the term chronic cough would be applied.  It has a reported prevalence of between 14% and 23% and is associated with morbidities including sleep loss, impaired performance of daily activities and urinary incontinence in women.1,3 The diagnosis and management of chronic cough are often unsatisfactory. In non-smokers with a normal chest radiograph, the most common causes are postnasal drip syndrome, gastroesophageal reflux disease and cough variant asthma, although other less common causes like angiotensin converting enzyme inhibitor (ACEI), foreign body, chronic bronchitis and lung carcinoma should be considered.3-6 Several algorithms have been developed for investigating the cause of chronic cough, involving a series of investigations, trials of empirical treatments or both. However, despite these attempts, in 12% to 31% of patients the specific cause of the cough is not established and despite extensive treatments no resolution is gained. Numerous therapeutic interventions have been tried in patients with chronic persistent cough.3 Examples include common antitussives like antihistamines and dextromethorphan, centrally acting antitussives (opioids and nonopioids), nebulized topical anesthetics/steroids, oral steroids, antireflux regimens, and behavioral cough control techniques. Unfortunately, when all of these approaches fail, there appears to be no remaining treatment option for chronic persistent cough.2 On the other hand, these days attention toward traditional medicine for the discovery of new sources of remedies for diseases has increased. In recent years, some experimental studies have indeed evaluated traditional Iranian medical remedies, using modern scientific methods. These studies raised the possibility of revival of traditional treatments on the basis of evidence-based medicine.7 Gelatin is widely used in traditional Iranian medicine for the treatment of chronic persistent cough. It is a high molecular weight polypeptide derived from collagen. Its industrial preparation involves controlled hydrolysis of the organized structure of collagen to obtain soluble gelatin. The sources of collagen for the gelatin production are bovine hide, bone and pigskin.8 In this article, we describe our experience with a group of patients with chronic cough and report on a new potential therapy for such patients based on gelatin.

 

 

Materials and Methods

 

This study is a randomized clinical trial study of patients seen at an outpatient clinic (Shiraz-Iran). Adults complaining from cough with duration of more than 3 weeks, either directly referring to the clinic or being referred by other physicians, were visited by the author from September 2006 till July 2007. A careful history was taken and they all were thoroughly examined. No patient had recently (within the past two years) smoked or used ACEI. No patient had any other signs and symptoms of lung disease nor any systemic signs and symptoms including fever, sweating or weight loss. Chest radiograph was taken to exclude pneumonia or other lesions in the lungs. Sinus CT scan was done to exclude chronic sinusitis. Informed consent was obtained from all the patients. 

Gelatin was obtained from one industrial source (Kaam Factory, Tehran, Iran) to guarantee its equality in all patients. The samples were sent to biochemistry laboratory (School of Medicine, Shiraz University of Medical Sciences) to validate their purity. Then 10 grams of gelatin was dissolved in 50 cc of tepid distilled water (about 35° C). The solution was then preserved in a dark glass in room temperature.

The patients who fulfilled the above criteria (100 subjects) were randomly divided into two equal groups. The first group was instructed to continue their previous antitussive medication which included loratadine, pseudoephedrine and inhaled corticosteroid, of course not the whole control group used all the above medications simultaneously. The second group was instructed to discontinue all their antitussive medications for 3 days and then start the gelatin solution 5cc (a teaspoon) three times a day. All the patients were then asked to refer to the author after 6-10 days to be re-evaluated and were instructed to immediately call the physician if their symptoms exacerbated.

After 6-10 days when the patients referred to the clinic, they were again thoroughly examined to find out any new clues for any diseases and then they were evaluated for their symptoms. Evaluation included subjective assessment of improvement by the patients themselves, their report of the percentage of reduction of the symptoms, and recording of side effects. The patients were asked to rate their cough  reduction on a 0% to 100% scale; no reduction was labeled as no response to therapy, 0%-25% as poor response, 25%-50% as fair response, 50%-75% as good response and 75%-100% as excellent response. The mean difference in the two groups was assessed by t-test and the association by chi-square test.  P-value less than 0.05 was considered significant. All statistical analyses were performed, using the software SPSS (Version 11.5, Chicago, IL, USA). 

 

 

Results

 

We screened 250 subjects during 11 months, 100 of whom met all the inclusion criteria and, therefore, were included in the study. In the second group, there were 23 women (46%) and 27 men (54%) with an age range between 21 to 70 years and a mean of 41.4 (standard deviation=14.7). The first group consisted of 26 women (52%) and 24 men (48%) with an age range between 22 to 71 years and a mean of 42.9 (standard deviation=12.8). Statistical methods showed no meaningful difference between the two groups for age (p=0.59) and sex (p=0.54).

Cough duration in the first group was 6.4 weeks in average with a standard deviation of 2.1, ranging from 3 to 12 weeks with a majority of 28%, having a5 week duration. As to the second group, the cough duration average was 6.4 weeks, ranging from 6 to 12 weeks with a majority of 26%, having a 6 week duration. The statistical analysis did not suggest any meaningful difference between the two groups (Table 1).

 

Table 1: Cough duration distribution in the studied groups

Group

Group 2

Group1

Abundance

No.

%

No.

%

3-5 weeks

22

  44

22

  44

6-8 weeks

20

  40

19

  38

9-12 weeks

  8

  16

  9

  18

Total

50

100

50

100

 

In the second group, after 6-8 days of initiation of the study, two subjects (4%) reported no response, 10 (20%) poor response, 16 (32%) fair response, 19 (38%) good response, and 3 (6%) reported excellent response. In the first group, 8 subjects (16%) reported no response to the therapy, 15 (30%) poor response, 14 (28%) fair response, 9 (18%) good response, and 4 (8%) excellent response. The mean improvement for the second group was 43.5% in comparison with 32.3% in the first group. No side effect was reported by either of the patients.

 

 

Discussion

 

Chronic cough management is a real challenge for physicians, putting a big burden on the patients.1,2 Considering its morbidities, any new safe therapy should be welcomed. Traditional medicine has always provided us with sources of treatment of different diseases.7 Recent experimental studies in traditional medicine including Chinese, Indian and Iranian have given proof to the usefulness of this rather poorly scientifically experienced area.7 Gelatin has been widely used in traditional Iranian medicine for the relief of chronic cough.  The mechanism is unknown, but it seems that it somehow affects the cough receptor in the pharynx. However, the safety of this substance made us experience its efficacy through a study. We first designed a randomized clinical trial study but we could not provide enough subjects to obtain a statistical significance. So, we designed the study with 100 patients we had during our one year visit. We randomized the subjects in two groups. The results obtained after the study, although not statistically reliable, are quite hopeful: the mean improvement in the second group is 43.5% compared to the 32.3% in the first group, and if we perform Mann-Whitney U test on the results of the two groups, the mean rank for the second group would be 51.93 compared with 49.07 of the first group which is higher (p value=0.60). This difference is not significant but is encouraging.

Despite the inadequate number of the cases studied, this difference in patients’ improvement -which as we said cannot be used to make a clear-cut conclusion- is a good indication that gelatin can be a promising treatment for chronic cough. So, we suggest that a larger scale study be designed to clearly investigate the effectiveness of gelatin for the treatment of chronic cough. Another limitation of our study is that we cannot exclude the placebo effect of gelatin. This can be further complicated when we come to this point that our measurement of cough improvement was based on a subjective criteria. So, larger controlled clinical trials with long term follow ups are needed to exclude the placebo effect and to minimize the effect of the subjective measurement of cough improvement.

Gelatin concentration is another issue to be discussed; we used a concentration that would create a liquid solution to ease its consumption but it is not a recommended concentration. The duration of gelatin consumption is also an issue to be considered; using Pearson Correlation Coefficient did not prove any relationship between the cough duration and gelatin use in the second group (p=0.3, r= -0.14) but the minus figure gives a hint that more gelatin could actually shorten the duration of cough (Table 2).

 

Table 2: Duration of gelatin usage in the second group

Usage(days)

No.

%

3

  9

  18

4

17

  34

5

18

  36

6

  3

    6

7

  3

    6

Total

50

100

 

The work presented here represents our short term experience with gelatin for chronic persistent cough.  Accepting all limitations of our study, we hope that it can be used as a ground for further studies.

 

 

Acknowledgement

 

We would like to thank Estahban Islamic Azad University for financial support of the project.

 

Conflict of interest: None declared.

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