Discussion
The concentration of salbutamol in the plasma was low following inhalation therapy delivery devices. LEWIS et al reported a median plasma concentration of 7.4 µg/l of salbutamol after one hour of inhalation through a nebulizer.22 At the same time, the concentration of salbutamol in urine following inhalation is much higher which becomes convenient to get detected through assay. Salbutamol is excreted majorly through the kidneys. The basic properties of salbutamol are unlikely to exhibit significant pH-dependent clearance through the renal system, especially pH values below 6.5 of urine.23
Hindle and colleagues established that the increased initial recovery of the drug is due to the fact the salbutamol delivered to the lungs was rapidly absorbed through alveoli and then eliminated unchanged by the kidneys.14 They employed this simple non-invasive method in 10 healthy subjects to determine an optimal inhaler technique with commercially available metered-dose inhalers (MDI) comparing different respiratory maneuvers. Later, this method has been used to compare the delivery of drugs to the lungs through different devices24 and evaluate the effect of inhalation rate.25 For the first time we employed this method to study the inhaler technique use among patients with obstructive pulmonary disease and correlate it with the control status of the disease.
The proportion of patients making inhaler errors differs widely between the studies and the estimated of those making inhaler errors ranges up to 90%26, 27. The strong correlation between inhaler device use and disease status is established through multiple studies. Incorrect use of devices may have an impact on the effectiveness of the drug delivery further leading to poor treatment outcomes.17 On the other side, improving inhaler technique through training led to significant improvement in the number of attacks (p<0.001), emergency applications, hospitalizations (p>0.05), and overall quality of life.28
Over half of the COPD patients were unable to use the device correctly.1 In a systematic reviewing 144 published articles on inhaler technique use and the errors made by the patients, only a low proportion (31%) of patients could demonstrate the correct inhaler technique.29 This concludes the correct use of inhaler technique has not improved over the past 40 years despite different approaches. In the present study, only 1 patient out of 30 could perform all the 8 steps correctly and half of them scored only ≤5 steps correct.
The mean urine concentration of salbutamol was found to be 3.6±1.6 µg/ml and the highest mean urinary concentration of salbutamol was found in patients performing all eight steps correctly. The mean difference in urine concentration of salbutamol was found to be steadily increasing with an increase in the total number of correct steps and it was found to be statistically significant (p=0.028). The mean urinary concentration of salbutamol was negligible (0.5 µg/ml) in patients reported with the highest exacerbation frequency. Similar results were reported by Molimard and colleagues, that those making critical errors in handling the device were likely to experience a two-fold increase in severe exacerbations than those who handle their devices without critical errors (3.3% versus  6.9% respectively).7
Previous studies reported poor inhaler technique led to inadequate drug delivery to the lungs can end up in an unintentional form of non-adherence. COHORT investigators reported unintentional nonadherence through poor metered-dose inhaler technique associated with overuse of ICS in mild to moderate COPD patients. ICS use was more common among patients with poor MDI technique (44%) than those with adequate technique (25%).30 We noted an inverse relationship between the prescribed frequency of short courses of OCS and antibiotics with a mean concentration of 30-minute urinary salbutamol over the previous 12 months. The mean difference in 30-minute urinary concentration of salbutamol and antibiotic use in the past year was found to be statistically significant. (p=0.032).