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).