Discussion
To the best of the authors’ knowledge, this is the first study that used clinical, spirometry and radiology data to comprehensively assess the prescribing pattern of inhaled pharmacotherapy and its related outcomes in an Aboriginal Australian population with chronic airway disease. This study highlights several key findings:
Almost 93% of remote residing Aboriginal patients with chronic respiratory conditions who were referred to the respiratory and sleep outreach service were noted to have been prescribed with one form or another airway directed inhaled pharmacotherapy.
ICS containing inhaled pharmacotherapy was by far the most frequently prescribed inhaled pharmacotherapy.
COPD was the most common condition recorded among study patients prescribed with inhaled pharmacotherapy, with the majority being prescribed LAMA or LABA either alone or in conjunction with ICS.
Irrespective of what impairment was observed on spirometry, ICS containing inhaled pharmacotherapy prescription is the most common.
ICS was observed to be prescribed in up to 76% of patients with bronchiectasis.
Patients with a prescription of ICS showed almost double the hospital admission rate, especially with COPD or bronchiectasis compared with asthma.
ICS prescription was also significantly associated with increased hospital admission rates secondary to lower respiratory tract infections.
Despite overwhelming evidence in the literature to indicate that chronic airway diseases are highly prevalent among Aboriginal/Indigenous people, not only among Aboriginal Australians,4–8 but also among other Indigenous people globally,31–36 there is little evidence in the literature examining the efficacy, safety or prescribing patterns and related outcomes of inhaled pharmacotherapy. Hence, the current study addresses this gap in knowledge and could be viewed as an invaluable addition to the literature.
In this study, we observed that COPD was the most common condition among patients being prescribed inhaled pharmacotherapy. This is not surprising though, as it reflects the high prevalence of COPD in the remote residing NT Aboriginal population, as well as the high smoking rates (>90%) noted in the current and previous studies.4–6 While there is evidence to suggest either LAMA or LABA in combination or in isolation are beneficial in the management of patients with COPD,37–39 the use of ICS in the management of patients with COPD is controversial and continues to be debated.40–42 In our study, the majority of patients diagnosed with COPD were observed to be prescribed with LAMA/LABA containing inhaled pharmacotherapy, in line with the beneficial outcomes noted in previous reports.37–39 However, a significant proportion of patients with COPD were also noted to be prescribed with ICS.
Among patients presenting with chronic airway diseases, spirometry alongside other clinical parameters, including exacerbation frequency are often used in clinical decision making, including when considering inhaled pharmacotherapy in day-to-day clinical practice.17 18 In the absence of spirometry reference norms among adult Indigenous people,43 there are substantial challenges in the accurate diagnosis and classification of the severity of airway disease,44 45 in order to guide inhaled pharmacotherapy appropriately. Health practitioners caring for Indigenous/Aboriginal people undoubtably rely on and adopt evidence established in non-Aboriginal/Indigenous ethnic populations that may or may not be appropriate for Indigenous/Aboriginal people. A previous study from our centre found that among Aboriginal patients with COPD, irrespective of which severity classification is used (GOLD, COPD-X or Global lung function initiative-2012), the majority of patients will likely be classified as having either severe or very severe disease.46 Hence why, with spirometry demonstrating a high proportion of patients classified to have severe COPD, and in line with current recommended guidelines,20 we observed a significant proportion of patients with COPD having an ICS prescription. However, a recent study has demonstrated that there could be excessive decline in lung function parameters, in particular for FEV1 values, associated with ICS use among Aboriginal Australians with chronic airway diseases.47 Hence, caution has to be exercised while considering ICS containing pharmacotherapy among an Aboriginal Australian population with a high prevalence of concomitant airway disease.
Use of inhaled pharmacotherapy may be appropriate among patients with asthma or selected patients with COPD,16–21 yet among those with bronchiectasis, consensus guidelines are far more individualised and depend on the frequency of exacerbations, prior medication response and comorbidity of asthma and/or COPD.48–51 As ICS reduces the local (pulmonary) immune response, there is potential for deleterious effect of ICS use among patients with bronchiectasis, as the disease is typically underlined by long term bacterial colonisation, perpetuating a vicious cycle of recurrent infective exacerbations and further airway inflammation, alongside a decline in lung function, which may be exacerbated by long term use of ICS.47 52 In our study, we noted a significant proportion of patients with underlying bronchiectasis had ICS prescribed—even in the absence of evidence of comorbid lung conditions—and moreover, patients prescribed with ICS had higher rates of hospital presentations. Hence, it may be reasonable to presume the overlap of bronchiectasis and ICS prescription could be at least partially driving the higher hospital admission rates seen among our patients. Contrary to international guidelines recommending against the use of ICS among patients with bronchiectasis unless there are clear clinical justification,53 ICS containing pharmacotherapy continues to be prescribed frequently/liberally even among the non-Aboriginal Australian population,54 with data suggesting unprecedently 6.3% of Australians have a current ICS prescription,55 potentially inappropriately in certain circumstances. Furthermore, more recent studies have raised serious concerns in relation to ICS use and its association with risk of pneumonia among patients with airway diseases, more specifically with fluticasone containing inhaled pharmacotherapy.56–59 The results of our study potentially add to this body of evidence, with the high rate of hospitalisations among patients with a prescription of ICS, and fluticasone was by far the single most prescribed ICS among our study participants.
The current study also found that ICS prescription, regardless of underlying respiratory condition, was associated with significantly higher overall hospital admission rates and more specifically with higher COPD with lower respiratory tract infection admission rates (ICD-J44.0), in particular in the presence of bronchiectasis. Due to the retrospective study design, we cannot ascertain if ICS prescription contributed to excessive hospital admission rates or if the excessive hospital admission rates triggered ICS prescriptions, and nor could the exact point of initiation of therapy compared with hospital or PHC presentations be determined accurately. Nonetheless, healthcare utilisation for respiratory disorders is generally observed to be higher for Indigenous people globally, especially in high-income countries such as Australia, New Zealand and Canada.14 60–62 It is unclear at this stage if the high healthcare utilisation rates observed are related to the adoption of therapeutic interventions established among non-Aboriginal/Indigenous populations, or if it is related to a higher prevalence of chronic and more severe respiratory disease burden.
Nevertheless, in the Australian context, it appears that inhaled pharmacotherapy is liberally and extensively used to treat chronic airway diseases among Aboriginal Australians, despite the lack of clear evidence or guidelines. Several previous studies have reported on the use of airway directed inhaled pharmacotherapy in other ethnic populations, indeed highlighting rather inappropriate prescribing patterns on several fronts, more particularly in the excessive use of ICS among patients with airway disease, including at the PHC level.63–66 This trend appears to be true for the current study, as we noted that inhaled pharmacotherapy prescribing patterns did not clearly align with spirometry results, particularly among patients demonstrating restrictive or mixed impairments. This is despite the Australian rural guidelines manual (CARPA) recommending to consider ICS only if the spirometry demonstrates BDR among patients with bronchiectasis.51 It is imperative to acknowledge that there are substantial differences in the way in which respiratory diseases manifests in Aboriginal people in comparison to non-Aboriginal Australian counterparts.67–77 In this vein, recent studies have recommended to take a personalised and tailored approach, by adopting clinical, spirometry and radiology in the accurate diagnosis, alongside advocating cautious use of inhaled pharmacotherapy in the management of chronic respiratory conditions among Aboriginal people.47 78 Moreover, following locally developed prescribing guidelines that have been specifically developed for patients residing in remote and rural communities is vital,51 in order to reduce treatment emergent morbidity and mortality.42 59 Currently, there is limited access to comprehensive medication review services for Aboriginal people79 and in remote communities.80 Studies have shown that the involvement of Aboriginal Health Workers and Consultant pharmacists can have a positive impact on appropriate prescribing patterns.81 82 These types of services could be established and evaluated in this setting.
Limitations
The authors acknowledge that this study has several limitations. The participants included in this study were drawn from referred patients to a specialist respiratory service in the TEHS region of the NT, hence, the outcomes represented in this study cannot be generalised, neither to other Aboriginal Australians residing in the NT nor to those living in other Australian states or territory or Indigenous people globally. The reason we observed a high proportion of patients being on inhaled pharmacotherapy is likely related to this. Moreover, medication adherence data were not available to be assessed, which would have had an impact on hospital and PHC presentations. Furthermore, spirometry, radiology and pharmacotherapy prescriptions did not all occur at the same time point, but rather were spread through the study window, and indeed some patients may have swapped between therapies and dosages in this time period, including during exacerbations, thus curtailing the potential for this study to truly assess any time course effect. In addition, medical services provision for patients residing in remote communities can be variable and transient, swapping between primary/visiting general practitioners/visiting specialist health work force, hence, choice and treatment initiation or ceasing are often dependent on the individual medical practitioner’s discretion. On a similar note, we did not collect data on length of hospital admission or care provided during hospital admissions, which may have affected propensity for future visits, nor the exacerbation history of the patient which limits our ability to define the appropriateness of+ICS prescription. In other underserved populations medication sharing is commonly reported, however, whether this is the case in the current population and study sample is not known. We also did not include or compare the prescribing practice between Aboriginal and non-Aboriginal patients in this study, in order not to introduce bias. As such, previous studies have demonstrated significant difference in the way chronic respiratory diseases manifests Aboriginal patients compared with non-Aboriginal Australians. Nevertheless, this is the first study to assess the prescription and associations of inhaled pharmacotherapy in a predominantly adult Aboriginal Australian population, highlighting opportunities for prospective further research to exploring avenues in the better management of chronic respiratory conditions.