Evaluation of bronchodilators and mucolytic agentsSR Kamat
Department of Chest Medicine, Seth G.S. Medical College and K.E.M. Hospital, Parel, Bombay-400 012, India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 458736
Source of Support: None, Conflict of Interest: None
Relief of dyspnoea or expiratory obstruction has been an important step in the management of chronic lung diseases. When there are other factors like ineffective cough, undernutrition, dehydration, infective exacerbations, these need specific measures. For the treatment of bronchospasm, bronchodilators have been very much in common use. A common way of judging their efficacy is to clinically monitor the frequency and severity of attacks to record changes in the clinical status and also to detect the degree of prolongation of expiration or wheezing. 
One way of objective evaluation has been to record the need of additional medications required. These can be suitably scored and can serve as an index of the efficacy of a drug. , So with effective drug the need for other medicines is minimised. A more objective way is to record changes in pulmonary function before and after the drug for a short study  and over a long period intermittently (say once weekly) for the long term effects. , The functional parameters measured may be FVC, FEV,, MEFR, PEF, DMBC and sometimes airway resistance, flow volume curves or blood gases.
The former are measured by a spirometer, peak flow meter and a weather balloon. The latter are recorded on a multichannel recorder with instantaneous monitoring of flow, volume and pressure curves. The patients chosen are those with regular attacks, evidence of obstruction on lung function and absence of infection. These methods can be applied to various old and new drugs and comparative efficacy worked out.
We did several comparisons of ephedrine-theophylline combinations. The long acting preparations gave a more sustained functional improvement .  Over 3 weeks there was little difference between the short and the long acting preparations for clinical improvement, the former being somewhat better. The combinations with prednisolone (6 mg.) and standard dose theophylline were more useful in maintaining the clinical and functional status.  However, low dose ephedrine-theophylline was not useful except for its prednisolone content. 
There was some evidence to show that prednisolone in small doses also increases gastric distress  and phenobarbitone does not seem to contribute usefully.  From our results there may be a case for omitting phenobarbitone totally from the bronchodilator preparations.
Parenteral steroids in a long acting preparation produce a sustained (upto 6 days) improvement in lung function an-4 clinical status, more so in asthmatic cases.  The peak effect was seen around the 3rd day and it did not change the incidence of lung infection,
When an intravenous preparation was given for acute study, the improvement in function was seen maximally at 4 to 6 hours.  Even theophylline alone showed bronchodilator effect only at 6 hours thus suggesting that its other effects are useful in giving relief in status asthmaticus.
In a crossover comparison of oral salbutamol (4 mg.) with ephedrine (30 mg.) given 4 times daily for 3 weeks it was shown that two drugs were comparable but there was a slight tolerance to ephedrine at 3 weeks.  A comparison of ephedrine-theophylline combination with salbutamol showed some superiority of the former. There was no evidence of residual long term benefit for lung function with either of the preparations. The relief with salbutamol thus was comparable with the traditional combination in a 3 months trial. 
The new beta stimulator drugs gave good improvement as aerosols. The latter when given by gas flow method are more effective than when given as the freon powered inhaler.  Salbutamol or isoprenaline were similar but the effect of the former was more sustained (for 4-6 hours).
Over a long term aerosol trial in (byssinotic) cotton mill workers, orciprenaline and salbutamol aerosols gave greater improvement as compared to placebo or isoprenaline. 
Further studies with salbutamol aerosol showed it to give improvement only during the few hours of administration , . Similarly many newer drugs can be evaluated by using these methods.
In a long term study of aerosolised sodium chromoglycate we found that only a proportion of asthmatic patients improved. (unpublished data). In a study of mucolytic drugs, we gave the drug as aerosol and showed in a study over 10 days that the drug reduced the viscosity of sputum but did not give much improvement of lung function. In fact, in some there was a decline in lung function after the drug. The functions were studied every hour for 8 hours for 8-10 days. There was a significant improvement clinically over saline aerosol in some cases. (under publication).
Thus new methods of assessment of bronchodilator drugs have changed our ideas about their role.