This study was undertaken in patients with productive and non productive types of chronic cough. The response to treatment with Diakof, a sugar free polyherbal formulation was evaluated for its effect in diabetic patients. These patients did not have symptoms suggesting variable airflow obstruction, and had normal spirometric values and peak expiratory flow variability, no airway hyper responsiveness or sputum eosinophilia (> 3%). Fifty-one patients with chronic cough were identified among 200 referrals. The patients were suffering from various upper and lower respiratory tract infections, but a majority of them had bronchitis. The patients were dispensed Diakof syrup at a dose of 2 teaspoonsful three to 4 times a day for 2- 3 weeks. The diabetic patients began to respond from the first week. 43% were totally relieved, 25.49% had mild symptoms and 17.64% had moderate symptoms, while cough persisted in 13.72%. After 15 days treatment, 76.47% of the patients were completely relieved, while3.92% of the patients had moderate symptoms and 13.72% had mild symptoms. In 3 patients who reported only marginal relief, adjuvant therapy had to be given for their ailments. In 8 of the patients who had a follow-up sputum analysis, the eosinophil count decreased significantly from 16.8% to 1.6%. Thus, Diakof can be a useful drug in treating symptoms of cough in diabetic patients.

Chronic cough is a common symptom in clinical practice, which if not treated may become refractory in nature. Some researchers have identified asthma, rhinitis, and gastroesophageal reflux (GER) as the most common causes of chronic cough^1-4. Frequently, patients have more than one of these conditions. The underlying mechanisms of cough in these conditions are not defined.

Hyperresponsiveness of the upper airway (UAHR) resulting from inflammatory mediator release could be a common mechanism of cough in these patients^5,6. The upper airway has abundant cough receptors, and stimulation of these receptors leads to cough, reflex laryngeal closure and intermittent upper airway obstruction. The release of inflammatory mediators⁷ could cause hypersensitivity of the upper airway to histamine, which is present in patients with symptoms resembling asthma (including cough), ACE inhibitor cough⁸ and in rhinitis. Inflammation is a feature of the most common conditions which are associated with chronic cough. In asthma and rhinitis, there is mucosal inflammation with eosinophils and mast cells^9-11. Proximal reflux of acid in GER results in posterior laryngitis¹² and hypersensitivity of the cough reflex¹³. In addition, ACE inhibition, which is also associated with chronic cough, and UAHR could enhance the tussive effects of tachykinins, which are normally inactivated by ACE in lung tissue¹⁴. The presence of inflammatory mediators in the upper airway could enhance the sensitivity of afferent nerves. Thus, it is hypothesised that airway inflammation induced by these diseases would cause hyper-responsiveness of the upper airway to histamine provocation and that this would be the unifying mechanism that explains the occurrence of chronic cough in asthma, rhinitis, GER and ACE inhibitor therapy.

The above symptoms can be controlled with different conventional formulations. However, in diabetic patients it has limitations because most of the available cough syrups contain sugar. Therefore a study with Diakof Linctus, a non-sugar formulation was conducted.

Patients with chronic cough lasting for more than 3 weeks were identified from new patient referrals made by primary care physicians in both rural and urban areas. The patients were aged between 28 and 76 years. The patients with chronic cough had no clinical or radiologic evidence of significant lung disease at the time of referral.

Thirty adult male and 20 female diabetic patients referred to the respiratory outpatient clinics with chronic cough as the predominant symptom gave informed consent to be enrolled in the study. All the patients had cough for more than 4 weeks and a normal chest X-ray prior to inclusion in the study.

The subjects had a full history taken and a physical examination was performed. The history was recorded on a standardized questionnaire, and previous medical problems, medications, smoking history, amount of sputum and hemoptysis were recorded. The primary diagnosis was rhinitis in 7, asthma in 9, post-viral-infection status in 5, bronchitis in 21, gastroesophageal reflux in 3, COPD in 1, bronchiectasis in 2 and ACE inhibitor-induced cough in 3. The cause of chronic cough remained unexplained in 5 patients (Table 1). Subjects rated the frequency, severity, and symptoms suppression related to cough using 4-point scale, where 0 corresponded to no symptoms, 1 to mild symptoms, 2 to moderate symptoms, and 3 to maximum symptom intensity. Complications of chronic cough, including rib fracture, syncope, headache, sleep disturbance, urinary incontinence and social disruption more recoded. Symptoms of intercurrent disease such as post-nasal drip, GER, and asthma were reported on the 7-point scale. A standard self-administered psychiatric symptom questionnaire (SCL-90R) was also administered. Sputum volume and the size and number of plugs were recorded. Clinical diagnoses were made according to the following criteria: rhinitis was considered to be present when there was a history of current (past week) symptoms of post-nasal drip, nasal stuffiness, or sneezing rated 4/7 on the 7 point scale; asthma was diagnosed when there was a history of cough and current variable airflow obstruction clinically, GE reflux was diagnozed when symptoms of indigestion and regurgitation of fluids and food were present at a severity of 4 on a scale of 1 to 7, sinusitis was diagnozed by a history of facial pain and a response to antibiotics. Subjects using ACE inhibitors, either recurrently or previously at the time of coughing were considered to have ACE inhibitor cough.

The cough was present for an average of 4-6 weeks. The majority of the patients had been on unsuccessful trials of medications, with 16 having received inhaled corticosteroids, 10 antibiotics, 6 inhaled b2 agonists, 7 histamine-type 2 receptor antagonists, 8 antacids, 6 oral corticosteroids, 4 inhaled cromoglycate, 2 nasal decongestants, 2 nasal corticosteroids, and 1 omeprazole. Most (38/51) patients had experienced several cough related complications. These included sleep disturbance (17/51), social disruption (16/51), urinary incontinence (5/51), presyscope (6/51), headache (15/51), syncope (2/51), back and chest pains (28/51), exhaution (10/51) and hoarseness of voice (8/51) (Table 2). These patients were asked to get their fasting and postprandial blood sugar levels checked till the end of the study period. They were also requested not to stop antidiabetic treatment for any reason.

The results showed that most of the patients responded well to the cough syrup. The patients who came for follow-up after a week reported that they had felt a soothing effect over the inflamed upper respiratory tract. Out of the 51 patients who came for follow up, 22 were totally relieved of the cough symptoms. However, they were advised to continue the medication for another 8 days. Thirteen patients had mild symptoms, 9 patients reported moderate symptoms and the symptoms of cough persisted in 7 patients. These patients were advised salt water gargle in addition to consumption of the cough syrup. After 15 days, 39 patients reported complete relief from chronic cough and were psychologically free from any symptoms. Seven patients had minimal cough occurring occasionally and continued the treatment till the symptoms disappeared totally. Two had moderate symptoms and 3 patients out of the 51 felt that the symptoms were still present and requested for additional medication (Table 3). They were prescribed additional oral antihistamine tablets along with Diakof syrup.

The cause or causes for chronic cough in most patients, confirming the diagnostic value of the anatomic-diagnostic approach was successful identified¹⁵. The treatment success rate of 90.19 % was very similar to those reported by Irwin and colleagues¹⁶ and others¹⁷ in a similar patient population, and was slightly higher than that reported by O'Connell and coworkers¹³ and McGarvey and associates¹⁸ in patients referred to a tertiary referral center. Thus, it was confirmed that rhinitis and bronchitis are common causes of chronic cough in this clinical setting. The modified protocol recognized bronchitis in 41.17% of patients. The occurrence of chronic cough due to gastroesophageal reflux as seen in this study is now well established, and mechanisms have been described by other authors¹⁹.

The data suggest that assessment of airway inflammation is an important addition to the algorithm for investigating chronic cough. The airway inflammation was assessed with induced sputum, since this method is noninvasive and has been shown to be successful in the majority of patients with asthma²⁰. Sputum differential cell counts have been shown to be valid and repeatable in patients with asthma²¹. Sputum induction is also successful in most patients with chronic cough, and that sputum eosinophilia is the only significant finding in 13% of cases of such cough. Although induced sputum was analyzed, spontaneous sputum could be used if patients have a productive cough. Differential cell counts are similar with the two methods, but the cell viability is greater and squamous cell contamination less with induced sputum, resulting in better quality cytospin preparations²².

The association between psychological symptoms and cough is interesting in this study. The validity of the relationship is supported by an epidemiological association between chronic cough and anxiety, and multiple case reports of psychogenic cough in the pediatric and adult literature^23,24. It is unclear, however, whether psychological distress is a cause or an effect of chronic cough. Persistent cough could contribute to excessive psychological distress because of its ability to disturb sleep, normal work and social activities. Further studies are needed to clarify these issues.

Diakof Linctus contains many herbs, which include Vitis vinifera, Ocimum sanctum, Tinospora cordifolia, Adhatoda vasica, Glycyrrhiza glabra, Balsamodendron mukul and others. The combined action of all these herbs provide anti-inflamatory and non sedating antihistaminic property to the linctus. Since diabetic patients with a long persistent cough have low immune status, herbs such as Tinospora cordifolia provide immune boosting properties.

The patients in the study presented with cough without wheezing, dyspnea, or objective evidence of variable airflow obstruction, and thus did not meet conventional criteria for the diagnosis of asthma. There was subjective improvement in the cough and a significant decrease in their sputum eosinophil count after treatment with Diakof. The improvement began within a week after the treatment begun.

In this study it was evident that diabetic patients can safely use Diakof Linctus for managing symptoms of cough. The blood sugar level remained constant throughout the study period. No untoward side effects were seen in any of the patients.