Asthma is a heterogeneous disease characterized by different underlying disease processes leading to airway inflammation and variable airflow limitation 1,3. As a chronic respiratory condition, it has a considerable impact on patient quality of life, with effects ranging from mild functional limitation to significant morbidity leading to prolonged hospitalizations. Due to its prolonged and far reaching effects on all aspects of the patient’s life, asthma has been ranked as the 14th most important disorder in the world, in terms of the extent and duration of disability associated with it 2. With a varied prevalence, ranging from 1-18% in most countries, it is considered to be one of the most common non-communicable chronic lung diseases 3.
Despite remarkable improvements in pharmacologic therapy, asthma management has remained a major challenge in developing countries where in addition to the rising level of pollutants, long term adherence to therapy and treatment fatigue have presented significant barriers to optimal health care 5.
Published guidelines recommend inhaled medications as the first choice for asthma treatment because they allow for a smaller dose of the drug to be deposited directly into the lung 5, 6 resulting in a rapid onset of action. However, effective drug delivery is contingent on correct inhaler technique 8. Previous authors have reported the prevalence of sub-optimal technique with metered-dose inhalers (MDIs) and dry-powder inhalers to be as high as 45% 9, resulting in reduced efficacy and an increase in adverse effects both of which ultimately lead to an increase in the number of emergency department visits 10,11.
Inhaler efficacy can be enhanced by the use of a spacer device. By allowing the medication to be held in the chamber long enough for patients to inhale slowly and deeply, a spacer effectively mitigates poor coordination between actuation and inhalation. This eliminates oral deposition of the medication, otherwise thought to be as high as 80% of the inhaled dose, increasing the efficiency of the inhaler 11.
The ultimate aim of asthma therapy is to achieve disease control along with minimal side effects and cost. These outcomes can only be achieved with appropriate prescription, therapeutic compliance on part of the patients and the correct use of inhalers. A shortfall in any one of these aspects of care results in suboptimal symptom control and can potentially initiate a vicious cascade of effects that may further compromise adherence to therapy.
In our study, we aim to explore the challenges faced by patients in the management of a non-communicable chronic lung disease like asthma, as well as the prevalence of poor inhaler technique and non-compliance with therapy. We also aim to identify commonly reported reasons for non-compliance with therapy so that effective strategies can be developed to eliminate them and ensure long term adherence to therapy, which would result in better quality of life for the individuals suffering from this chronic debilitating condition.
Materials and Methods:
This prospective cross-sectional study was conducted at the Chest clinic of Aga Khan University Hospital (AKUH), Karachi, Pakistan. AKUH is a 496-bedded tertiary care center, located in the city of Karachi, which has a multi-ethnic population of roughly 17.6 million people, as per the World population review. Although the patient population attending our facility primarily comprises of middle/upper income-class groups of the city, referrals are seen from health care centers across the country. The chest clinic which is conducted six days a week is staffed by six full time and two part-time consultant respiratory physicians with approximately fourteen thousand patients attending the clinic each year. Most of our patients pay out-of-pocket for consultation with the physician as well as the medications. Approval for this Research Protocol was obtained from The Hospital Ethics Committee. For the purpose of this observational study, we have followed the STROBE guidelines and checklist 26.
Our study population included patients who were at least 12 years of age, using MDIs with or without a spacer for 6 or more weeks and formally diagnosed with Asthma by a consultant respiratory physician. Recruitment of study participants began in August 2009 and lasted for six months. Following an outpatient consultation with the specialist, a trained junior doctor or respiratory nurse specialist invited patients to visit an adjoining room to participate in a structured questionnaire based face-to-face interview and undergo inhaler technique assessment with either an MDI alone or a combination of MDI and spacer if prescribed. For patients with multiple follow-ups during the study period, the first visit was used for inclusion/analysis.
The study questionnaire consisted of two parts. The first part focused on patient demographics, duration of illness, duration of inhaler use, prior formal inhaler teaching as well as medication being taken up until that particular hospital visit. The second part was related to a set of self-reported questions regarding adherence to prescribed regimen over the preceding 6 weeks and included the following questions; “Have you taken all your inhaler medications in the last six weeks?”, “If no, how often did you miss your medication?” with available options “daily”, “once a week”, “more than once a week”, “Why did you miss your medication?” with available options “side effects”, “forgetfulness”, “cost”, “improved symptoms”, “concern about addiction”, “Do you feel you are using the inhaler correctly?” and “Do you see any mist escaping when you use your inhaler?”.
An assessment of the inhalation technique was performed by asking the patients to take 2 puffs of an MDI alone or an MDI using a spacer for those who had been prescribed one, while being observed by the researcher. Inhalation technique of the study participants was evaluated based (table 1) on the recommendations by the National Institutes of Health review committee for the treatment of asthma13.
For study purposes, the following were considered to be asthma medications: inhaled short-acting beta2-agonists (SABA), oral short-acting beta2-agonists, inhaled long-acting beta2-agonists (LABA), inhaled corticosteroids (ICS), inhaled anticholinergics, methylxanthines, leukotriene receptor antagonist and oral steroids. In case of combination therapy, each active ingredient was counted separately.
Analyses were performed using the Statistical Package for Social Sciences (SPSS) version 19 (Chicago, IL, USA). A descriptive analysis was performed for the demographic profile. Results were presented as the Mean ± Standard deviation for quantitative variables and a number (percentages) for qualitative variables (gender, co-morbid conditions, drugs). Univariate and multilevel regression models were used to explain variability in prescribing, self-reported compliance and inhaler technique with age, gender, prior inhaler teaching or the number of prescribed medications. All p-values were two-sided and considered statistically significant if <0.05. Results: During the study period, 202 patients with asthma were studied prospectively. Mean age ±SD of the study participants was 49.41 ±17.9 years. Nearly half of all subjects were female (n=106, 53%) and a large majority (n=179, 88%) hailed from urban areas. Around one-tenth (n=24, 11%) were found to be current smokers and slightly more than a quarter (n=51, 29%) of the participants reported exposure to passive smoking. 107(53%) patients reported having had asthma for >4 years, 59(29%) between 1-4 years and slightly less than a fifth (n=36, 18%) reported having had Asthma for <1 year (Table 2). Only 41(20%) participants reported having pets at home, which mostly included dogs. Less than one-third of the (n=59, 29%) patients were able to correctly use an inhaler device with (n=37, 40%) and without a spacer (n= 22, 22%) respectively. Of the 168(83%) participants who had previously received formal teaching, only 49(29%) could perform all the steps correctly. Approximately half the cohort(n=97, 48%) had been prescribed a spacer with their inhaler and a larger proportion of these individuals was able to demonstrate the correct use of the combination compared to those prescribed a simple MDI i.e. 40% vs. 22% respectively, which was found to be statistically significant(p<0.05)(figure 1). However, less than two thirds (n= 61, 60%) of the study participants reported the frequency of spacer use as 'every time'. Even though nearly three quarters (n=143, 70.8%) of the patients perceived their technique to be 'satisfactory', a major proportion of these individuals (n=100, 69.9%) did admit seeing fumes when using the inhaler. When using an MDI without a spacer, the three steps where mistakes were made most frequently were found to be; "begin a slow breath" (n=49, 47%), "waiting 30 seconds before next actuation" (n=44, 46%) and "hold breath ? 4 sec" (n=41, 42%) (Figure 3). Whereas, when using an MDI with a spacer, the three most frequently identified mistakes were "hold breath ? 4 sec" (n=42, 41%), "waiting 30 seconds before next actuation"(n=41, 40%) and "actuate the MDI once" (n=35, 34%) (Figure 3). More than one-third (n=78, 39%) of the cohort self-reported being non-compliant with inhaler use in the last six weeks (table 1). Of these, 18 (9%) reported missing them daily, 34 (17%) once a week and 26 (13%) more than once a week (figure 2). Reasons for not taking their medication regularly were cited as (figure 2) improvement in symptoms (n=32, 16%), forgetting (n=23, 11%), side-effects (n=16, 8%) fear of dependence (n=6, 3%) and cost (n=1, 0.5%). Age, gender, number of prescribed drugs or prior inhaler teaching did not predict non-compliance. The three most commonly prescribed drugs (table 3) were salbutamol (n=124, 61%), salmeterol/fluticasone combination (n=112, 55%) and beclomethasone (n=52, 26%) respectively. Two-thirds (n=133, 66%) of the patients had been using inhalers for >12 months (table 1). Inhaled corticosteroids (ICS) were prescribed in a large majority (n=178, 88%) with no age or gender discrimination (table 3). Approximately a third were on single (n=70, 35%) and dual (n=74, 37%) drug therapy each, while only 11(5%) of the patients were found to be taking 4 or more drugs (table 3). Around two-thirds (n=129, 64%) of patients said they would discuss their medication only with the doctor, with an additional 50(25%) who were happy to discuss it with their nurse as well. Only 23(10%) patients reported being comfortable discussing their therapy with anyone else, including the shopkeeper/pharmacist.
Inhaled therapy remains the most effective and important aspect of asthma maintenance treatment for patients of all ages6,8. The therapeutic benefit of this mode of delivery is dependent on sufficient deposition of medication in the medium-sized and smaller airways, which is largely determined by a competent inhaler technique and holds true for inhalers of all designs and complexities12. Globally there are variations in prescribing practices for asthma and these have been ascribed to differences in the case mix of patients, socioeconomic factors, and availability of different inhaler and spacer devises locally 13. At the time of this study simple MDIs where the only type of devices officially marketed in Pakistan and majority of them were not CFC-free.
Guidelines for the management of asthma 14,15stress the use of therapy with inhaled corticosteroids for disease control. Treatment algorithms emphasize chronic maintenance therapy over acute episodic care and emphasize the need for its daily use in an effort to decrease morbidity and mortality rates 16. In our study, encouragingly a large majority (n=178, 88%) of the patients were found to have been prescribed an inhaled corticosteroid. However, only about two-thirds of these patients (n=101, 67%) reported using them regularly. In contrast to previous studies 4, a short-acting beta2 agonist inhaler (n=124, 60%) or its combination with a corticosteroid (n=14, 7%) was found to have been prescribed less frequently (table 3). This, we believe is primarily due to the easy availability of nebulizers and nebulized medications. Access to nebulized reliever medication often eliminates the need for patients to seek emergency medical care in the event of an exacerbation, reducing their health related costs. Alarmingly however, only 14% of the patients who had been prescribed inhaled SABA’s were found to be using them on an as needed basis, while a significant proportion of the patients prescribed SABAs reported having been advised to use them between once a day to every 6 hours (n=119, 86%). The regular and continued use of this class of medications has in past raised concerns about an associated unrecognized decrease in their efficacy and a potential delay in seeking medical attention during periods of exacerbation 16, both of which lead to adverse health outcomes and extended hospital stays.
As with any chronic disease, patient compliance is an important determinant of therapeutic success. Haynes and Sackett defined compliance more than three decades ago as “the extent to which a person’s behavior (in terms of taking medications, following diets, or executing lifestyle changes) coincides with medical or health advice.” 18 Creer et al 19 divided factors that correlated with non-compliance into four categories: patient variables, interactions between physician or medical staff and patients or family, medication characteristics, and nature of asthma. Additionally, Cochrane20 described several patterns of noncompliance including taking only half of the medications at the prescribed times, taking regularly for a period and stopping, and skipping prescribed doses. In line with previously published data, more than a third of our patients (n=79, 39%) reported not being compliant with their medication in the preceding six weeks. Commonly reported reasons for non-compliance included improved symptom control and simply forgetting (figure 2). Noncompliance was found to be significantly higher in women (n=46, 58%) as compared to men (n=33, 41%). We believe that both these findings reflect the importance of asthma education in predicting compliance to the prescribed medication regimen. Patients who have been educated regarding the natural history of the disease are less likely to cease controller inhaler therapy, simply because of improved symptoms. To this day, female patients continue to have limited access to healthcare professionals in most parts of the city, and thus have barely been educated about asthma, beyond what they have learnt from their male counterparts or other patients.
Previous studies have reported a high rate of incorrect inhaler technique with MDIs and dry-powder inhalers (DPIs) 9. In our study, 71% of the patients demonstrated an incorrect inhaler technique. Although no significant association was identified between the prevalence of poor technique and the variables age, gender, previous inhaler teaching and length of inhaler use (figure 1), the use of a spacer with the inhaler was found to be associated with a significantly lower rate of poor technique, which reinforces the role of spacers in patient populations such as ours, who may find it difficult to administer the inhaler correctly otherwise. Unfortunately though, only about two-thirds (n=60, 61%) of the patients admitted using the spacer every time they used the inhaler, with approximately one fifth using it “occasionally” (n=19, 19%). Similar to earlier published data, incorrect slow inhalation technique was the most common mistake (n=49, 47%) made by patients using a simple MDI20. With the MDI+spacer combination, “holding breath at maximum inspiration” (n=42, 43%) was the most frequently identified error (figure 3).
Poor inhaler technique coupled with an inability to identify incorrect use can negatively impact patient compliance by causing them to incorrectly label their medications as ineffective and discontinuing treatment altogether 8. In our study, more than two-thirds (n=143, 70%) of the patients perceived their inhaler technique to be satisfactory, but nearly three fourth (n=100, 71%) of these also admitted to regularly observing fumes leaking around the inhaler during use. Interestingly, prior inhaler teaching showed no significant correlation with self-assessment of inhaler use or reporting of fumes escaping on use, implying poor retention of previous training and reinforcing the recommendations of previous studies that suggest regularly revisiting inhaler techniques with patients dependent on inhalers 8. It is equally important to periodically evaluate the inhaler techniques of healthcare providers who have been entrusted with the task of educating the patients, and retraining them if necessary, as previous studies have shown an increase in inpatients having their inhaler technique assessed and corrected, following such interventions 23. Patients with better knowledge and skills are likely to be much more confident and willing to undertake inhaler technique education to patients 24.
Our study has several limitations. Firstly, although the collection of data was standardized, some of it was based on self-reporting and thus a recall bias exists for such variables. In addition, a more detailed review of the patients’ educational background could have allowed us to investigate the association between literacy and poor retention of inhaler technique. Among the reasons for non-compliance, further inquiring into the patients’ knowledge and perceptions of medication side effects could have helped identify misconceptions so that these may be targeted in particular, as part of asthma education sessions. Also, since the data collected was primarily pertaining to asthma and did not take into account co-morbid conditions, patient reporting may have been affected. For instance, given that a quarter of our patients were current or ex-smokers, a possibility of concomitant COPD exits, but we believe that this would not impact our overall conclusions. Lastly, this was a single center experience and may not be generalizable to other institutions.