Objective: To assess and document the real-life efficacy and tolerability profile of “Haleezy” – a combination herbal product – in prevention of exacerbation (flares) and maintenance of remission in patients with bronchial asthma of mild to moderate severity.
Setting: Private practice clinics of 180 GPs from various cities and towns in our country.
Design: Phase IV open, multi-centre, observational, prospective study carried out as per Good Clinical Practice (GCP) guidelines using protocol, patient screening forms, patient’s written informed consent (ICF), patient case papers and case record forms (CRFs).
Patients: 1773 patients between 18-45 years of age with bronchial asthma of mild to moderate severity requiring anti-asthmatic treatment. All patients were required to sign written informed consent form prior to enrolment in the study to document their willingness to participate in the study as planned (as per protocol).
Intervention: Tablet Haleezy in a dose of 2 BID for 2 months: concomitant treatment with bronchodilators (b-agonist and methylxanthines) and steroids, were permitted where necessary. During acute attacks or exacerbations, bronchodilators were used as “rescue” medicines.
Outcome measures: The principal outcome measure in this study was the control of signs and symptoms of bronchial asthma and tolerability of study medication. The signs and symptoms that were evaluated included cough, dyspnoea and wheezing. At the end of the study period of 8 weeks, patients and treating physicians evaluated the global response to treatment - both for efficacy parameters and tolerability – as excellent, very good, good, average, poor, very poor.
Results: A total of 1773 case record forms were received. 59% of the patients were males while the rest were females. 40% of the patients reported history of acute asthma attacks. Treatment with Tablet Haleezy resulted in a statistically significant reduction in the severity score for cough, dyspnoea and wheezing (5.67 to 1.96, 5.73 to 2.2 and 5.07 to 2.62, respectively). Similarly, a significant reduction was observed in the pulse rate and the respiratory rate. Along with the decrease in the signs and symptoms of bronchial asthma, a corresponding decrease was also observed in the frequency of attacks. The efficacy of the study medication in the treatment of bronchial asthma was rated as either very good or good by the treating physicians in 71.6% of the cases. Similarly, the tolerability of Tablet Haleezy was rated as excellent, very good or good in 75.3% cases.
Conclusion: The study documented that Haleezy, a combination product of natural herbs, provides the desired symptomatic relief in patients with bronchial asthma. The symptoms of cough, wheeze and dyspnoea improved from the first follow-up visit (after 2 weeks of treatment). Continuing treatment until the end of study period produced further gains in relieving symptoms. Therefore, in the usual recommended dose of 2 tablets twice daily, Haleezy prevents acute attacks and prolongs the interval between two acute episodes. It also decreases the need for regular use of bronchodilators and/or steroids. Besides proving effective, Haleezy is well tolerated. The excellent efficacy and toleration of Haleezy was confirmed by both patients and their physicians.
Asthma is a disease of human respiratory
system characterized by narrowing or consriction of airways; there is accompanying inflammation and production of excess mucus. All this occurs in response to one or more “triggers,” such as exposure to an allergen, cold air, exercise, or emotional stress. It is imperative to understand that asthma is a “chronic” (reccurring) inflammatory condition characterized by bronchial hyper-responsiveness (the airways develop increased responsiveness to various stimuli) together with inflammation, increased mucus production, and intermittent airway obstruction.
Bronchoconstriction leads to symptoms such as wheezing, shortness of breath (dyspnoea), coughing and chest tightness; in most patients all of these symptoms are relieved with bronchodilators. It is important to understand that between ‘episodes’ or ‘acute flares’, however, many patients feel fine. Severity or intensity of symptoms of asthma are varied and may range from being mild to life threatening. Lifestyle changes and combination of drugs are required to help the asthmatics lead a near normal quality of life (QOL).
Current research suggests that the prevalence of childhood asthma has been on the rise. According to the Centers for Disease Control (CDC) and Prevention’s National Health Interview Surveys, in 2001, 9% of US children below 18 years of age had asthma compared with just 3.6% in 1980 (Up nearly 3 times). The World Health Organization (WHO) reports that incidence and prevalence of asthma among Swiss population has nearly quadrupled over last 2-3 decades - 8% compared with just 2% some 25–30 years ago.1 Further, the WHO estimates that there are between 15 and 20 million asthmatics in India.1 Also, globally, asthma claims around 180,000 lives annually.1 Therefore, due to its rapidly increasing prevalence, public attention has recently been focused on asthma.
Material and Methods
This Phase IV (Post-marketing) Multi-centre, Prospective Clinical Study was carried out in private practice clinics of 180 GPs, each of whom were required to study and document the effects of Haleezy (a combination herbal product) in 10 patients suffering from asthma of mild or moderate intensity. The objective of the present study was to assess and document the efficacy and tolerability of Haleezy in providing desired relief and maintaining the Quality of Life.
Patients of either sex between 18 and 45 years of age, suffering from bronchial asthma (mild to moderate severity) requiring long-term maintenance therapy were enrolled in the study. The purpose of the study was explained to every patient entering into this study. S/he was thereafter required to sign a written informed consent expressing the willingness to participate in this study.
Those suffering from acute asthmatic attack or heart failure or patients with hepatic / renal impairment were excluded. Also excluded were those with respiratory infections and pulmonary tuberculosis, as were patients unwilling to sign Informed Consent Document (ICD).
History and examination and visit schedule
A detailed history, including family history of asthma and allergies, past history of asthma - number and frequency of acute attacks, and interval between acute attacks - and treatment taken for it in the past was recorded. History of smoking was specifically enquired into, as was the occupation.
At each visit, symptoms of cough, dyspnoea (difficulty in breathing), wheeze and tightness of chest were scored as absent (0), mild (1), moderate (2) or severe (3) together with findings of general systemic examination (pulse, BP etc).
Eligible, enrolled patients were administered Tablet Haleezy in a dose of 2 tablets twice daily. Whenever required, concomitant treatment with bronchodilators (b-agonist and methylxanthines) and steroids (oral/inhalation) were allowed.
During the study period (8 weeks), each patient was required to follow-up every 2 weeks. At every visit, symptom scores, together with symptomatic relief obtained, were noted. Also, spontaneously occurring adverse event(s) was recorded with nature, intensity, duration, treatment taken and outcome.
During an acute attack or flare, patients were free to use bronchodilators and/or steroids as “rescue” medicines. The number, frequency and time interval between such attacks were recorded, as was the need for ‘rescue‘ medicines.
Patients were free to continue the study medicines beyond 8 weeks; however, such use was beyond the scope of this study.
Efficacy variables or assessment of response
Patients were asked to follow-up at fortnightly intervals. At each visit, compliance to treatment was recorded by noting the tablets “missed”, if any. Further, any unused tablets were counted and number of tablets used was corroborated. Also, the need for “rescue medicines”, if any, during the fortnight was recorded.
The patient’s assessment of symptom relief – cough and dyspnoea - was recorded as absent (0), mild (1), moderate (2) and severe (3), together with symptom-free period. Findings on examination of chest (wheezing) were also monitored.
Side effects, if any, were recorded with nature, intensity, action taken and outcome.
|Fig. 1 : Sex distribution of patints
||Fig. 1 : Sex distribution of patints by vocation
Of the 1800 case papers and CRFs, 1773 were received back and only 27 CRFs were not received back. All were used for efficacy and tolerability assessment.
Most patients were males (59%) while 39% were women (Fig.1).
Fig. 2 shows the distribution of patients by vocation. Most patients (29%) were at home (Household), while the number of Office-goers and students were nearly similar (12%).
46% patients were smokers (Fig. 3), while nearly 43% patients gave history of exposure to triggers (Fig. 4).
As shown in Fig. 5, 40% patients gave positive past history – acute episodes requiring treatment with steroids / bronchodilators.
|Fig. 3 : Smokers in study population
||Fig. 5 : Past history of acute attacks
|Fig. 4 : History of "triggers"
Efficacy of Tablet Haleezy on Cough
Administration of Tablet Haleezy showed a statistically significant reduction in the severity of cough across all age groups irrespective of smoking status, presence/absence of triggering factors and family history of asthma. The mean score of cough severity decreased from 5.67 in the first visit to 1.96 in the sixth visit. The reduction in the score was statistically significant (p < 0.05, Friedman Two-way ANOVA test). The Wilcoxon Matched-Pairs Signed-Ranks Test also indicated a statistically significant reduction in the cough severity score (p < 0.05).
Efficacy of Tablet Haleezy on Dyspnoea
A statistically significant reduction in the severity of dyspnoea was observed across all age groups with the administration of Tablet Haleezy irrespective of smoking status, presence/absence of triggering factors and family history of asthma. The mean score of severity of dyspnoea decreased from 5.73 in the first visit to 2.2 in the sixth visit. The reduction in the score was statistically significant (p < 0.05, Friedman Two-way ANOVA test). The Wilcoxon Matched-Pairs Signed-Ranks Test also indicated a statistically significant reduction in the dyspnoea severity score (p < 0.05).
Efficacy of Tablet Haleezy on Wheezing
Treatment with Tablet Haleezy resulted in a statistically significant reduction in the severity of wheezing across all age groups irrespective of smoking status, presence/absence of triggering factors and family history of asthma. The mean score of severity of wheezing decreased from 5.07 in the first visit to 2.62 in the sixth visit. The reduction in the score was statistically significant (p < 0.05, Friedman Two-way ANOVA test). The Wilcoxon Matched-Pairs Signed-Ranks Test also indicated a statistically significant reduction in the wheezing severity score (p < 0.05).
Along with the decrease in the signs and symptoms of bronchial asthma, a corresponding decrease was also observed in the frequency of attacks.
Effect of Tablet Haleezy on Pulse Rate and Respiratory Rate
Administration of Tablet Haleezy resulted in a statistically significant reduction in the elevated respiratory rate and pulse rate. The respiratory rate decreased from a mean of 25.61 ± 9.03 at visit 1 to 19.31 ± 3.97 at visit 6. The reduction in the respiratory rate was statistically significant (p < 0.05). Similarly, the reduction in the pulse rate was also significant (from 82.79 ± 10.2 at visit 1 to 77.61 ± 7.18 at visit 6).
Global Evaluation of Efficacy and Tolerability by Physicians
The efficacy of Tablet Haleezy in the treatment of bronchial asthma was rated as either very good or good by the treating physicians in 71.6% of the cases. In 10% of the cases, it was rated as average (Fig. 6).
Similarly, the tolerability of Tablet Haleezy was rated as excellent, very good or good in 75.3% cases, whereas it was rated as average in only 6.1% of the cases (Table 1).
|Fig. 6 : Global evaluation of the efficacy of tablet haleezy by the treating physicians
Evaluation of Efficacy and Tolerability by Patients
Almost 78% of the patients rated the efficacy of Tablet Haleezy as either excellent, very good or good. Similarly, almost 75% of the patients rated its tolerability as either excellent, very good or good. Less than 3% of the patients reported the tolerability of the study medication as poor or very poor.
No serious side-effects were reported with the administration of Tablet Haleezy.
The current therapy for bronchial asthma has several limitations. Further, like most patients suffering from “chronic” disorders, many asthmatics use alternative treatments; surveys show that roughly 50% of asthma patients use some form of unconventional therapy.2,3 Several studies suggest that various yoga practices such as, integrated yoga programmes4 — "yogasanas, Pranayama, meditation, and kriyas”—and sahaja yoga,5 do provide certain degree of relief to asthmatics.
Several natural herbs contain ingredients with documented benefits in relief of cough and wheezing in asthma. These benefits are possible due to their effects on coughing, mucus secretion and their anti-inflammatory effects. Haleezy is one such combination herbal product containing useful herbs such as - Adhatoda vasica (Vasa), Solanum xanthocarpum (Kantakari), Piper nigrum (Marich), Glycyrrhiza glabra (Yashtimadhu), Curcuma longa (Turmeric or Haldi), Terminalia belerica (Baheda) and Ocimum sanctum (Tulsi).
After it became known that asthma is a result of inflammation of respiratory passages, several studies have explored the use of known anti-inflammatory agents in providing the desired symptomatic relief to patients with asthma. Several reports from peer-reviewed journals have documented benefits of use of different herbs in treatment of asthma.
Adhatoda vasica (Vasa) has been shown to decrease severity and frequency of coughing and control the mucus discharge.6 According to a report from the journal Phytotherapeutic Research, Adhatoda vasica exhibits wide spectrum of medicinal properties including anti-inflammatory action7 and good anti-tussive activity.8
Haleezy also contains Solanum xanthocarpum (Kantakari). Its activity in treatment of mild to mderate bronchial asthma was compared with a known bronchodilator salbutamol. Solanum xanthocarpum produced progressive improvement in lung function of asthmatics over 3 days and the scores for rhonchi, cough, dyspnoea and sputum decreased significantly.9 Solanum xanthocarpum clearly exhibits bronchodilator effect as was seen from improvement in PEFR and reduction in other scores. Further, Solanum xanthocarpum was well tolerated and no untoward effects were reported.
Piper nigrum (Marich) was investigated for its anti-inflammatory properties and it was shown to possess significant anti-inflammatory activity.10 Besides, it is known to exhibit adaptogenic potential with possible immunostimulation,11 providing benefits on several counts for asthmatics – an ailment with genetic predispostion and history of allergy. It is known that asthma is a complex disease that is influenced by multiple genetic, developmental, and environmental factors, which interact to produce the overall condition.
Haleezy contains another useful herb - Ocimum sanctum (Tulsi). A report from our own country has shown that Ocimum sanctum also possess significant anti-inflammatory activity against PGE,2 leukotriene and arachidonic acid-induced inflammation (paw oedema). Ocimum has the capacity to block both the cyclo-oxygenase and lipo-oxygenase pathways of arachidonic acid metabolism to produce beneficial effects in inflammation.12
Glycyrrhiza glabra (Yashtimadhu) is known to suppress activities of 5-lipoxygenase and cyclo-oxygenase enzymes, key enzymes for production of pro-inflammatory cytokines that produce oedema and increased secretions.13 Thus, by interfering and blocking the synthesis of prostaglandins and leukotrienes, Glycyrrhiza glabra does provide benefits in asthma.
Curcuma longa (Turmeric or Haldi) has been known to Indians since centuries. Haldi has been a known household remedy for several ailments. It has been purported to have anti-inflammatory actions.14 Anti-asthmatic property of Curcuma longa has been tested in experimental animal model of airway hyperresponsiveness and has been documented to be effective in improving the impaired airways features.15 A study from Journal of Alternative and Complementary Medicine confirms that curcumin is safe in several human trials and inhibits a number of pro-inflammatory mediators that play an important role in asthma.16
Thus, Haleezy, a combination herbal product, has several useful herbs that work synergistically to provide the much desired control of inflammation and relieve symptoms of cough and expectoration whilst improving pulmonary function. Importantly, all the herbs are well tolerated, and are remarkably free of side effects that often limit the use of modern medicines.
To summarize, Haleezy – a combination product containing several useful herbs – does provide the desired symptom relief in asthmatics. Further, besides being effective it allows to avoid or minimize the use of modern medicines, which carry certain drawbacks and limitations, especially side effects, tachyphylaxis and difficulty with proper use. Haleezy taken in the usual recommended dose will be a very useful addition to the therapeutic armamentarium of asthma treatment filling the long desired gap.
The authors thank Charak Pharma Pvt. Ltd. for providing the drug Haleezy.
- World Health Organization. Bronchial asthma: scope of the problem Retrieved on 2005-08-23.
- Blanc PD, Trupin L, Earnest G, et al. Alternative therapies among adults with a reported diagnosis of asthma or rhinosinusitis: data from a population-based survey. Chest 2001;120(5):1461-7.
- Shenfield G, Lim E, Allen H. Survey of the use of complementary medicines and therapies in children with asthma. J Paediatr Child Health 2002; 38 (3) : 252-7.
- Nagendra HR, Nagarathna R. An integrated approach of yoga therapy for bronchial asthma: a 3-54-month prospective study. J Asthma 1986; 23 (3) : 123-37.
- Manocha R, Marks GB, Kenchington P, et al. Sahaja yoga in the management of moderate to severe asthma: a randomised controlled trial. Thorax 2002; 57 (2) : 110-5.
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- Indian J Exp Biol 1998; 36 (10) : 1028-31.
- Roum Arch Microbiol Immunol 2003; 62 (1-2) : 117-29.
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- J Altern Complement Med 2003; 9 (1) : 161-8.