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11th May 2023
Professor Adel Mansur specialises in asthma, leading one of the largest severe asthma clinics in the UK. Here, he discusses the centre’s involvement in primary care diagnostic hubs and his most recent practice-altering research.
Adel Mansur is a consultant physician at University Hospitals Birmingham NHS Foundation Trust and honorary professor in respiratory medicine at the University of Birmingham. Originally from Libya, where he attended medical school, Professor Mansur completed a research PhD in asthma genetics at the University of Leeds and joined Heartlands Hospital as a consultant in 2002.
Asthma is where Professor Mansur’s specialist interest lies, and he leads the trust’s severe asthma service – one of the largest and busiest centres of its kind in the UK, serving a local population of over 1.5 million and a regional population of 7.3 million.
We are a regional hub centre for severe asthma, so we receive referrals from across the region, from the West Midlands and beyond. Because of that, it’s a busy centre. There are currently just over 1,000 patients with severe asthma seen at the hub, and on a weekly basis we see 50 to 60 patients. We have a multidisciplinary team looking after our patients, comprised of doctors, specialist asthma nurses, physiotherapists, psychologists and speech therapists.
Our service is geared to deal with the complex and multifactorial disease of difficult to treat asthma, which forms a minority group of all asthma. However, most patients with asthma in primary care have mild or moderate disease but still many remain uncontrolled due to inadequate access to good quality diagnostics and treatment optimisation rather than because of disease severity. On this basis, we piloted with our primary care colleagues in Birmingham a respiratory community diagnostic hub. This provided a service of high-quality diagnostic and specialist input to optimise treatment and triage patients when necessary to our severe asthma network. We were pleased with the pilot outcomes, which led to its adoption by NHS locally and was also quoted by NHS England as an exemplar model.
We believe that we have now a good integrated pathway model in our locality to build on. The University Hospitals Birmingham NHS Foundation Trust still, however, receives 2,000 admissions every year due to asthma – the majority of which would be preventable with proper management in the community, thus arguing for increased capacity of this service model.
In many respects what we’re trying to do is to filter out those who are sub-optimally managed before they come to us. However, poorly controlled asthma can become severe, and that’s the danger that people will end up with sub-optimally managed disease that deteriorates to become more severe. It’s about being able to find those patients first, and that’s what the diagnostic hubs are doing.
Uncontrolled asthma is serious on its own because patients are exposed to potentially fatal attacks. A study looking at fatality in asthma found almost 60% of patients who sadly died from asthma attacks did not have severe asthma, but instead had uncontrolled asthma and weren’t on appropriate medication. This is a major current issue for which there are guidelines aimed at improving asthma management and outcomes. However, the implementation of such guidelines has been a challenge across the board, although I believe that progress has been made in terms of recognition of this issue and provision of clearer asthma management pathways for patients.
When you’ve optimised patients with uncontrolled asthma, you are left with around 10-20% who have severe asthma and will need, for example, a biologic treatment. For the majority of the others, regular preventer inhalers are usually adequate to control their asthma.
I would say up to 90% of asthma is a primary care issue that, with the right treatment and support, should be controlled. Those patients’ management would be best served in the community and wouldn’t require referral to come to severe asthma centres.
Yes, for example we have a research fellowship where junior doctors could do research with us as well as getting clinical experience. That could be for year, or two or three. We have visitors from different disciplines who come to sit in our clinics and shadow our multidisciplinary team members for experience. They’re not just doctors, we have visitors from various disciplines including pharmacists, physiotherapists, speech therapists and nurses who come from primary or secondary care, or even tertiary severe asthma centres, looking for exchange of expertise. We currently have a pharmacist from Saudi Arabia spending three years with us doing his PhD on treatment adherence in severe asthma.
At Heartlands, we have a respiratory research clinical trials unit, where we take part in various clinical trials that include cystic fibrosis, COPD, interstitial lung disease, occupational lung disease, asthma and some other acute presentation conditions such as pneumonia. It’s an active and large R&D department, so there are many other disciplines. Sometimes there is some overlap with other departments, for example, research into infectious diseases, Covid and viruses.
Primarily, I do clinical work, but I take part in research as an academic as well. With clinical work you have more direct interaction with patients, and more insight into patients’ needs. We can use that to explore the main research questions, and that will lead to conducting trials or taking part in studies locally. That could be through collaborations with other centres, either in the UK or internationally.
We then apply that in the clinic because clinical trials allow us to adopt cutting-edge treatments for our patients. They allow us to take the lead in providing our patients with access to cutting-edge and novel treatments, which, in many ways, transform the lives of many of our patients.
We developed in-house an assay for measuring prednisolone and cortisol simultaneously in the blood using high-performance liquid chromatography and spectrometry methodology. There are currently about four centres in the UK who provide this test clinically.
One of the issues in severe asthma is that 40% of patients are on oral maintenance steroids, and we assume that if a patient is prescribed 30mg prednisolone daily, for example, that is what they take. But with the assay we developed, we could actually look for adherence to prednisolone. We’ve done a case-controlled study using this assay among patients who are on steroids and patients who aren’t. We found that 40% of patients who are meant to be on maintenance steroids are not taking it. The assay results from non-adherent patients were similar to those who were not on maintenance prednisolone.
Now, we use the assay in practice and around our network, and it has been advocated by NHS England as well. We don’t really want our patients to be on maintenance steroids because there are newer treatments available now, and steroids are a legacy treatment that should be a last resort.
But we still have a substantial number of patients who are prescribed maintenance steroids, and knowing if they are taking the treatment or not is crucial – if they’re not we’ll stop the prescription of prednisolone and look for other treatments. The assay has also proved useful in managing adherent patients by allowing us to taper the prednisolone dose in a more controlled way. So, this is an example of something we developed here that has been quite crucial for the way we manage our severe asthma patients.
We have a registry for all of our severe asthma patients. There’s a local one and a national one, and the registry nationally produced more than 20 papers in good-impact journals in the last 10 years or so. One of the recent publications, of which I was the primary author, was on the UK practice of biologics in asthma. It looked at variation in practice between different centres, using registry data. We also looked at the outcomes of various biologics and observed that seven to eight in 10 patients do get a worthwhile benefit from biologic treatments.
The aim of having the registry for severe asthma is to promote standardisation of care across the country as well as cross-learning between different centres and adding to debate. We complemented the severe asthma registry analysis with a survey of specialists across the UK. We asked specialists why they choose a certain biologic over others, and which one they would start with and why, and we found variation in practice. It largely stems from the fact that there wasn’t a head-to-head trial to say one biologic is better than another one.
There is always going to be unmet need. We are not going to run out of jobs here, that’s for sure! One thing is the adherence issue, either to a biologic or to other preventer treatments. As humans we don’t like to adhere to things consistently. Some people can master it, but a lot of us can’t. So how can we really help people to have a treatment regime that works for them, and which they can maintain?
There are things like the interconnected digital inhaler, with sensors connected to the inhaler itself, which we are working on. I feel future practice in severe asthma will mean that the majority of patients will have smartphone apps with sensors connected to their inhalers. They’ll have their management plan and their treatment records on their app, which the physician can see on a separate platform, so we know when there are gaps in treatment.
The cost of severe asthma management to health services is high. Ensuring basic treatment in the form of regular use of preventer inhaler therapy may prove effective in controlling asthma without the need to escalate to expensive biologic treatment, as well as reducing burden to the NHS through a reduction in emergency room visits and hospital admissions. The adoption of digital inhalers as routine in severe asthma services is likely to be a much cheaper way of making sure patients’ disease remains under control. I think most severe asthma patients should be, at least in part, on this type of electronically monitored treatment.
Another unmet need is biologics – we still don’t have long-term data on those. I have seen patients whom, after two or three years, will have a viral illness or other trigger and then they feel the treatment is not working as it used to be. Or they suddenly start to flare up, so we look at switching biologics. Sometimes that works, but why does it happen in asthma? Why do some people have a super response, like remission, while others have had some response but still get exacerbations, and they still have residual disease of significance?
We have patients who have not been lucky enough to get a biologic treatment because of their disease type. They are not what we call T2-high, which is a type-2 inflammation that responds well to currently available biologic agents. About 20-30% of patients within the service are in this T2-low class, and these are the ones for whom there is unmet treatment need. Unfortunately, the asthma-related clinical outcomes of this group of patients remain significantly worse than those who could have, and respond well to, biologic treatments.
Things have moved on hugely in terms of the availability of good treatment for patients with severe asthma since I started practising 20 years ago. Our main treatment was lots of steroids, which, as lifesaving as they are, have short- and long-term serious side effects. We then had other things of questionable efficacy such as continuous terbutaline infusion. Nowadays, treatment for severe asthma has been transformed by a precision medicine era with the development of effective yet safe treatment options in the form of biologic treatments. There are currently six NICE-approved biologics and these cover around 60-70% of patients with severe asthma.
Tremendous progress has been made in dissecting the immunological cascades and mechanistics of inflammation in asthma. This provided plethora of therapeutic targets with many currently being trialled for asthma in general and severe asthma in particular. For example, there is a drug called masitinib, which is a tyrosine-kinase inhibitor that is being trialled as a possible treatment for asthma. Another example is the ongoing trialling of JAK-family inhibitors as a treatment option in asthma.
In addition to us being the hub here at Heartlands, we created a severe asthma network that included various centres – or spokes – within the West Midlands, Derbyshire and Gloucestershire, which covers a total population of 7.3 million people. Currently, the network is comprised of about 10 spokes. The spokes can initiate biologics in their respective hospital following approval from a monthly conducted regional multidisciplinary meeting with the hub. This model increased our region service capacity so patients can get the treatment in a quicker time and could have it initiated closer to home than if all patients have to travel to the hub in Birmingham.
This model provided resilience to service delivery due to the high number of asthma specialists included in the running of the service. We have 10 physicians, for example, and more than 10 nurses, who serve the network, contrasted to a small group in any single centre. So, that has been one of the strong points for our service – having a good, strong network. We are maintaining the quality through the performance and standardisation of patients being presented. That’s led to a successful network. It’s still a work in progress, as always, but we think we have good infrastructure.
Asthmatics have a higher risk of developing cancer, though use of inhaled steroids may have a slight protective effect, according to a US study.
Globally, cancer is the leading cause of mortality, with nearly 10 million recorded deaths in 2020. Data suggests that infection and inflammation contribute to a quarter of all cancers. In fact, the inflammatory milieu within a tumour seems to be an indispensable participant in tumour progression. In asthmatics, the inflammatory nature of their condition increases the risk of lung cancer. Nevertheless, other data either demonstrate a positive association or no association with the risk of other cancers.
In the current study, researchers sought to better understand the relationship between asthma and cancer risk. They analysed electronic health records in a US claims database. The team developed a matching cohort of those with and without asthma which served as the control group. Using regression models, researchers searched for any relationship between asthma and the subsequent development of cancer. The primary outcome was the time to a cancer diagnosis after the date of an asthma diagnosis.
The asthma cohort included 90,021 individuals matched to 270,063 without the disease. In multivariable analysis, asthmatics were more likely to develop cancer (hazard ratio, HR = 1.36, 95% CI 1.29 – 1.44). For example, significantly higher risks were observed for melanoma, blood, kidney and lung cancers. However, in contrast, risks were non-significant for bladder, colorectal and prostate cancers.
In a separate analysis examining the effect of inhaled steroid use, the overall cancer risk was slightly lower among steroid users (HR = 1.60 vs 1.11, inhaled steroid vs no steroid). Taken together, cancer risk was higher for nine of 13 cancers in asthmatics not using inhaled steroids but in only two cancers among steroid users. These findings suggest a possible protective effect of inhaled steroid use on cancer risk that requires further evaluation.
10th May 2023
There are several recognised co-morbidities associated with obesity including hypertension and asthma. In addition, the accumulation of more fat mass, is strongly associated with functional limitation among those with COPD. Moreover, other data suggest a positive association between abdominal obesity (AO) and asthma. This association appears to apply equally to both sexes. But whether abdominal or general obesity has a stronger association with either asthma or COPD is unclear.
The Respiratory Health in Northern Europe (RHINE) III study explored the independent association of abdominal and general obesity with asthma and COPD. In addition, the researchers examined any sex-related differences in these associations. In a cross-sectional study, the team used self-measured waist circumference (WC) as an index of AO. General obesity (GO) was a BMI ≥ 30.0 kg/m2. For the purposes of the analysis, a WC > 102 cm in males and ≥88 cm in females defined AO. Participants completed several questionnaires asking about respiratory symptoms and directly about a diagnosis of asthma and COPD.
Abdominal obesity and asthma or COPD
The study included data from a total of 12,290 participants of whom, 34.7% had AO and 6.7% GO. Abdominal obesity independently associated with the presence of wheeze (adjusted odds ratio, aOR = 1.40, 95% CI 1.24 – 1.58). This independent relationship was also present for GO (aOR = 1.96, 95% CI 1.70 – 2.27). There was a significant association between asthma and both AO and GO. In contrast, the association was only significant between COPD and GO (aOR = 2.14, 95% CI 1.54 – 2.99).
In relation to sex-related differences, asthma significantly associated with both AO (OR = 1.56) and GO in women (OR = 1.95) but not in men. This association also applied for COPD.
2nd May 2023
Respiratory syncytial virus (RSV) is a viral pathogen leading to acute lower respiratory infection in young children. Global estimates suggest that the virus causes 6·6 million infections in those aged 0 – 6 months and over 45,000 deaths. Whether RSV infection during this crucial period of lung development could subsequently lead to asthma is uncertain. INSPIRE was a surveillance study including children with or without an RSV infection (RSVI) during infancy. Monitoring of children took place over the next 5 years. The main hypothesis was that avoiding an RSVI during infancy reduces the risk of childhood asthma. The primary outcome was 5-year current diagnosed asthma and finding from the INSPIRE study have been recently published.
RSV infection and development of asthma
A total of 1741 children had available data during the first year of life. Among the entire cohort, 54% had an RSVI during that first year.
Over the next 5 years, not having an RSVI gave rise to a 26% lower risk of developing asthma (relative risk, RR = 0.74, 95% CI 0.58 – 0.94, p = 0.016). The authors estimated that 15% (95% CI 2·2-26·8) of current 5-year asthma cases could be prevented by avoiding a RSVI.
The researchers commented that among healthy children, not being infected with RSV in the first year of life was associated with a substantially reduced risk of developing childhood asthma. However, they recognise that their study was unable to establish a causal relationship.
13th April 2023
According to Chinese researchers and based on an analysis of individuals in the UK Biobank, having a healthy sleep pattern appears to mitigate the effect of genetic susceptibility to asthma.
Asthma is a chronic respiratory inflammatory disease and which globally, has been estimated to affect between 9.8 and 17.9% of the population depending on whether the definition includes wheezing or ever wheeze. Although there are a number of potential causes of asthma including a family history and exposure to various allergens, the presence of a persistent short sleep duration is one factor identified as being associated with an increased risk of developing asthma. While genome-wide association studies have revealed some asthma loci, the variability of genetic influence suggests that several other, non-genetic exposures may also influence the development of asthma.
In the current study, researchers examined the association between sleep traits, genetic susceptibility and the risk of asthma in a UK Biobank cohort. The team undertook an analysis of those aged 38-73 years and for whom polygenic risk scores and comprehensive sleep scores, were constructed. The researchers used a multivariable Cox proportional hazard regression model to investigate the independent and combined effects of sleep pattern and genetic susceptibility on asthma incidence. Participants were assigned as being at a low, intermediate and high risk of asthma based on genetic susceptibility and sleep categorised as ‘healthy’, ‘intermediate’ and ‘poor’.
Healthy sleep pattern and development of asthma
From a total of 455,405 individuals with a mean age of 56.5 years (54% female), 17,836 were diagnosed with asthma during over 10 years of follow-up.
Compared with those deemed to be a low genetic risk, the hazard ratio (HR) for those with the highest genetic risk was 1.47 (95% CI 1.41 – 1.52) for the development of asthma. Similarly, among those with poor sleep, there was also an elevated risk for asthma (HR = 1.55, 95% CI 1.45 – 1.65). In addition, among those with a high genetic risk and categorised as having poor sleep, there was a more than two-fold increased risk of developing asthma (HR = 2.22, 95% CI 1.97 – 2.49, p < 0.001).
However, in further analysis, researchers found that a healthy sleep pattern was associated with a lower risk of asthma in all three genetic susceptibility groups. For example, a healthy sleep pattern reduced the risk of developing asthma by 44% (HR = 0.56) among those at a low genetic risk and by 37% in those at high genetic risk (HR = 0.63). In fact, the researchers calculated that at the population level, a low genetic risk and a healthy sleep pattern could reduce the risk of asthma cases by up to 19%.
The authors concluded that a healthy sleep pattern reflected a lower risk of asthma in adult populations and could be beneficial to asthma prevention regardless of genetic conditions.
Xiang B et al. Highlighting the importance of healthy sleep patterns in the risk of adult asthma under the combined effects of genetic susceptibility: a large-scale prospective cohort study of 455 405 participants. BMJ Open Respir Res 2023
19th February 2023
A study analysing hospital admissions for both chronic obstructive pulmonary disease (COPD) and asthma from 1999 to 2020, has revealed a significant increase for both conditions despite a considerable increase in prescribed treatments for these diseases.
Both COPD and asthma are common respiratory diseases. In a recent global systematic review it was estimated that some 391·9 million people had COPD in 2019 and the World Health Organization (WHO) estimates than in 2019, there were 3.23 million global deaths from COPD. Asthma also affects a huge number of people and WHO estimated that in 2019, the disease affected some 262 million people across the world and led to 455,000 deaths. With both diseases leading to a considerable number of deaths, in the present study, a team of Saudi Arabian researchers examined the trends in hospital admissions and which could result in death, for both COPD and asthma between 1999 and 2020. The researchers extracted information from the hospital episode statistics database in England and the corresponding database was Wales. In addition to hospital admissions data, the team also collected information on COPD and asthma-related medicines prescribed between 2004 and 2020.
Hospital admissions for COPD and asthma
The total annual number of admissions for the two conditions rose by 82.2% between 1999 and 2020 which represented a 59.1% increase in the hospital admission rate over this period of time (p < 0.05).
The most common reason for COPD admission (38.7%) was in combination with an acute lower respiratory tract infection and which increased by 198.5% between 1999 and 2020. In contrast, acute exacerbations of COPD alone, accounted for a quarter of admissions (25.5%) and this rate had actually reduced by 4.8% between 1999 and 2020. As with COPD, asthma additions also increased by 46.1% over the 21-year period.
Just over a third (34.7%) of COPD and asthma admissions occurred in those age 75 years and older with just under a quarter (23.5%) in those aged 15 – 59 years. Interestingly, slightly more than half (53.8%) of admissions for both conditions occurred in women.
When looking at prescriptions, the researched observed a 42.2% increase the absolute number of COPD and asthma-related dispensed medicines between 2004 and 2020, which represented a 27.2% increase between the two periods of time (p < 0.05).
The authors concluded that while the data showed a clear rise in hospital admissions for both conditions the reasons behind these increases were unclear and they called for further research to try and better understand the factors responsible for these higher rates.
Alwafi H et al. Trends in hospital admissions and prescribing due to chronic obstructive pulmonary disease and asthma in England and Wales between 1999 and 2020: an ecological study. BMC Pulm Med 2023
3rd December 2021
The effectiveness of allergen immunotherapy (AIT) in allergic rhinitis (AR) patients both with and without asthma has been confirmed in a 9-year retrospective analysis by researchers from the Paediatric Pulmonology and Allergy, Children’s Doctor Service, Heidelberg, Germany.
Allergies represent an abnormal immune system reaction to otherwise harmless allergens and in the UK, AR is estimated to affect 10-15% of children and 26% of adults. In addition, patients with AR can also suffer with asthma as a co-morbidity, with studies suggesting that 10% to 40% of AR patients have asthma. Furthermore, the presence of AR is associated with an incremental adverse impact on the disease-specific quality of life in patients with asthma and the level of asthma control.
Allergen immunotherapy (or desensitisation treatment) involves exposure to increasing doses of an allergen such as grass pollen, dust mite, or cat dander. AIT can be given via the subcutaneous or sublingual route, both of which have been shown to be effective treatment for patients with AR. Nevertheless, there is a recognised lack of information from studies on the effectiveness of AIT in real-world studies and over the longer term.
In order to address this gap in the evidence, the German researchers undertook the Real World effectiveness in allergy immunotherapy (REACT) study, primarily to assess the efficacy of AIT over a period of years. Using a retrospective, observational, propensity score matched cohort study, the team analysed health insurance claims from 2007 to 2017 and included AR patients with and without asthma and who had received an AIT prescription. These individuals were then propensity-score matched with AR individuals (also with or without asthma) but who had not been prescribed AIT. The primary outcome of the study was set as AR prescriptions in each follow-up year and secondary outcomes included asthma prescriptions, severe asthma exacerbations and any changes in the individual’s asthma treatment steps.
Between 2007 and 2017, 115,098 individuals had at least one AIT prescription, of whom, 46,024 with a mean age of 29.5 years (53% male) were propensity score matched. In addition, 14,614 AR patients with AR and co-existing asthma (mean age, 28.3 years, 54% male) were also matched with controls. However, over the 9 years, the study population declined, leaving 3692 individuals in the main cohort and 1142 with co-existent asthma.
When compared to control patients, AIT use was consistently associated with greater reductions in both AR and asthma prescriptions. In addition, there was a significantly greater likelihood that patients using AIT would have an asthma treatment step-down (p < 0.0001) and a reduction in severe asthma exacerbations (p < 0.05).
The authors concluded that their study had confirmed the real-world effectiveness of AIT as evidenced by sustained reductions in AR and asthma prescriptions, prevention of asthma exacerbations, and improved and sustained long-term asthma control.
Fritzching B et al. Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study. Lancet Regional Health Europe 2021
14th September 2021
Asthma is caused by inflammation and a narrowing of the small airways and leads to the symptoms of cough, wheeze, shortness of breath and chest tightness. According to figures from the World Health Organisation, in 2019, globally, an estimated 262 million people had asthma and the condition resulted in 461,000 deaths. Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death and in 2019 led to 3.23 million lives lost. Inhaled medication is the most common medical intervention used to control the symptoms of both asthma and COPD and effective management of both relies upon patients having the correct inhaler technique. However, in a 2016 systematic review, it was found that the prevalence of a correct technique was only 31%. Furthermore, in a 2018 review of inhaler errors in both asthma and COPD, found an association between inhaler errors and worse health outcomes, highlighting the importance of having some form of inhaler technique service. In fact, studies have shown that an inhaler technique service to asthmatic patients improved both inhaler technique scores and disease control.
Exacerbations of both asthma and COPD can result in hospitalisation and a team from the Department of Medicines Management and Pharmacy Services, Leeds Teaching Hospital, Leeds, UK, examined the impact of an inhaler technique service on respiratory wards. Included patients were those admitted to hospital with an exacerbation of either asthma or COPD at the teaching hospital in Leeds and the service was provided by pharmacy support workers. Using an inhaler standards and competency document, the staff scored inhaler technique as optimal, satisfactory or unsatisfactory. Patients whose technique was deemed unsatisfactory or satisfactory received training from the pharmacy staff and where necessary, recommended to prescribers that an inhaler device should be changed. The outcomes of interest were the rate of moderate-to-severe exacerbations of asthma and COPD and hospital admissions due to such exacerbations, in the six months prior to and after receipt of inhaler technique training.
The inhaler technique service was provided to 266 patients with a mean age of 60.5 years (53% female), of whom 28% had asthma. Each patient was prescribed a mean of 2.3 inhalers and a total of 616 inhaler technique assessments were undertaken during the study period. Inhaler technique at baseline was deemed optimal in 28.6%, satisfactory in 49.4% and unsatisfactory for 22.1%. After training, the proportion of patients whose technique was deemed optimal increased to 91.5%. These improvements were achieved from a change of inhaler device (21.8%), optimising therapy without a change of device (34.9%) with the remainder due to training with the same device.
Six-month exacerbation and hospital admission data were available for 164 (62%) of all patients. Following the inhaler technique service and compared to pre-service levels, there was an overall and significant, 37% reduction in the mean number of exacerbations over a 6-month period (risk ratio, RR = 0.63, p < 0.05). This reduction occurred for both asthma (RR = 0.58, p < 0.05) and COPD (RR = 0.66, p < 0.05). Similarly, the overall rate of hospital admissions was also significantly reduced (RR = 0.56, p < 0.05) and again this occurred for both conditions. In addition, the inhaler technique service reduced the average length of hospital stay and cost of hospital admission for disease exacerbations.
The authors concluded by recommending that a ward-based inhaler technique service should be a core component of the care of patients with asthma and COPD.
Capstick TGD et al. Ward based inhaler technique service reduces exacerbations of asthma and COPD. Resp Med 2021