Expert Review of Respiratory Medicine ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ierx20 Multidisciplinary consensus on inhaled therapy in asthma Antonio L. Valero, José A. Trigueros & Vicente Plaza To cite this article: Antonio L. Valero, José A. Trigueros & Vicente Plaza (2021) Multidisciplinary consensus on inhaled therapy in asthma, Expert Review of Respiratory Medicine, 15:3, 425-434, DOI: 10.1080/17476348.2021.1841639 To link to this article: https://doi.org/10.1080/17476348.2021.1841639 © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Published online: 10 Nov 2020. Submit your article to this journal Article views: 1733 View related articles View Crossmark data Citing articles: 1 View citing articles Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=ierx20 EXPERT REVIEW OF RESPIRATORY MEDICINE 2021, VOL. 15, NO. 3, 425–434 https://doi.org/10.1080/17476348.2021.1841639 ORIGINAL RESEARCH Multidisciplinary consensus on inhaled therapy in asthma Antonio L. Valeroa, José A. Triguerosb and Vicente Plazac a Allergy Unit, Pneumology Department, Hospital Clínic, IDIBAPS, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; bMenasalbas Primary Health-Care Center, Toledo, Spain; cDepartment of Respiratory Medicine, Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomédica Sant Pau (IIB Sant Pau), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain ABSTRACT ARTICLE HISTORY Background: Asthma is managed by health professionals from different specialties. We aim to reach Received 21 August 2020 a consensus on the optimal use of inhaled therapy and the initial steps of asthma treatment, taking into Accepted 21 October 2020 account the opinions of the involved specialists. KEYWORDS Methods: A modified Delphi approach was used. A scientific committee provided 52 controversial Asthma; breath-actuated statements, which were submitted to primary care physicians, allergists, and pulmonologists. inhalers; consensus Discrepancies among specialties were evaluated. Results: A total of 209 specialists completed the questionnaire (20.2 ± 9.3 years of asthma management experience). A consensus was reached on 37 statements (71.1%), discrepancies among specialties were found in 14. The most recommended maintenance treatment for mild persistent asthma in adults/ adolescents was low-dose-inhaled corticosteroids daily. MART (Maintenance and Reliever Therapy) was recommended as salvage treatment for moderate persistent asthma. Panelists agreed on the most frequent critical errors with pressurized Metered-Dose Inhalers or Dry-Powder Inhalers, and considered that Breath-Actuated Inhalers are a suitable option for all patients with the ability to inhale voluntarily. Conclusions: The experts endorse the main guidelines recommendations; however, do not fully agree on recent GINA recommendations about the treatment of the initial steps of the disease. The experts value positively the differential characteristics of BAI over other devices. 1. Introduction treatment, which account for the majority of patients [6–9]. Furthermore, asthma is a heterogeneous disease and is man­ Asthma is estimated to affect 235 million people worldwide aged by various health professionals, such as primary care [1]. Despite the advances in recent years in the pathophysiol­ physicians, allergists, or pulmonologists. Although, the main ogy of the disease, and especially in its treatment, it is esti­ asthma guidelines are similar for all health professionals, the mated that less than 50% of asthmatic patients have their views of the different specialists involved in the management disease under control [2]. Among the causes of poor control of asthma may differ, since the type of patients they attend, are possible concomitant diseases and aggravating factors, and the available resources they have, are different. lack of adherence, inadequate treatment or poor inhaler tech­ Considering all these difficulties and disparities in asthma nique [3]. management, the objective of this work is to reach Inhaled therapy is the cornerstone of asthma treatment, a multidisciplinary consensus on the optimal use of inhaled however, it is associated with various disadvantages that therapy in asthma and on the treatment of the initial and may decrease its effectiveness. One of the main drawbacks intermediate stages of the disease, taking into account the lies in the difficulty that many patients have in using inhaler views of different specialties involved in the asthma patients devices correctly [4]. Therefore, patients must be trained to care. use them correctly. In addition, many recent studies have shown that the level of knowledge of health professionals about the theoretical and practical aspects of inhaled therapy 2. Patients and methods may be insufficient [5]. The existence of multiple devices for In this project, a consensus methodology based on a modified administration of inhaled therapy, each with its own particula­ Delphi technique has been used, following the UCLA/RAND rities, can make it difficult for health professionals to know recommendations [10,11]. them in depth. Additionally, although there are rigorous evi­ dence-based clinical guidelines for the management of As a first step, a scientific committee, consisting of 3 asthma, not all of them are homogeneous in their recommen­ asthma experts (from primary care, allergy, and pulmonology), dations, especially at the initial or intermediate stages of met to develop a Delphi questionnaire based on a non- CONTACT Vicente Plaza VPlaza@santpau.cat Department of Respiratory Medicine, Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomédica Sant Pau (IIB Sant Pau), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona 08041, Spain * These authors contributed equally to this work. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. 426 A. L. VALERO ET AL. communication (in a journal or in a conference) or one training Article highlights session on asthma as a tutor in the preceding year. The pane­ ● This multidisciplinary consensus brings together the opinion of lists were active members of scientific societies and were per­ a large number of specialists from different specialties on the optimal sonally invited by the scientific committee. use of inhaled therapy and the initial steps of asthma treatment. The questionnaires were submitted to the panel online in ● This multidisciplinary group of experts endorsed the main recom­ mendations on education and adherence proposed by national and two rounds (during November and December 2019, respec­ international clinical practice guidelines but did not fully agree on tively). The items were evaluated using a 9-point Likert ordinal recent GINA recommendations about the treatment of the initial scale (1 = strongly disagree; 9 = fully agree). The responses steps of the disease (intermittent and mild persistent asthma) regard­ ing the PRN use of low-dose ICS/formoterol combination as the were grouped into 3 categories (1–3 = disagree; 4–6 = neither preferred option. agree nor disagree; 7–9 = agree). Consensus on an item was ● The most recommended maintenance treatment for mild persistent reached when (1) the median of the responses fell within the asthma in adults/adolescents was low-dose-inhaled corticosteroids daily. 7–9 category (consensus on agreement) or within the 1–3 ● MART (Maintenance and Reliever Therapy) was recommended as category (consensus on disagreement); (2) less than one- salvage treatment for moderate persistent asthma. third of the panelists voted outside these categories, and (3) ● The experts valued very positively the diverse characteristics of BAI and their advantages over other inhaler devices. the interquartile range of the responses (IQR) was lower than 4. Items for which an agreement was not reached in the first round were reevaluated in a second round of voting. Between rounds, panelists were informed of the detailed distribution of the responses from the first analysis. Panelists who did not systematic exhaustive literature search and their own exper­ respond to the first round were excluded from a subsequent tise in the management of asthma. The three experts (VAL, TJA questionnaire assessment. and PV) are prominent members of their respective scientific Results are shown in tables as median and interquartile societies (the Spanish Society of General and Family Doctors range (IQR) of the responses. Tables also show: (1) the percen­ [SEMG], the Spanish Society of Pulmonology and Thoracic tage of panelists in the median region, which was defined as Surgery [SEPAR], and the Spanish Society of Clinical the percentage of panelists who voted within the category Allergology and Immunology [SEAIC], respectively), and key that included the median of the responses (1–3, 4–6, or 7–9), members of the committee that develops the Spanish Asthma and (2) the final results of the consensus: agreement or dis­ Guidelines (GEMA) [9]. Literature search included recent agreement in the 1st or 2nd round, or no consensus. asthma management guidelines and the following terms in Once the general analysis was carried out, a post hoc PubMed in the last 5 years: Asthma, Asthma/Therapy, Inhalers, analysis of the responses by specialties (primary care, allergy, Nebulizers, and Vaporizers, Dry Powder Inhalers, Metered Dose and pulmonology) was performed to evaluate the degree of Inhalers, Breath-Actuated Inhalers, Treatment Adherence and consensus amongst them. Compliance, Patient education, Self-care, Self-management. After several meetings in person, the scientific committee reached an agreement on the content of the questionnaire. 3. Results It included statements focused on controversial or unan­ swered questions about the optimal use of inhaled therapy A total of 209 panelists answered the questionnaire. Panelists in asthma, and on debatable recommendations given in the had a mean of 20.2 ± 9.3 years of experience in managing guidelines about the treatment of the initial or intermediate asthma patients. Mean number of follow-up of asthma con­ stages of the disease. sultations per month was 69.5 ± 68.6 (primary care physicians: The questionnaire consisted of 52 items divided into 6 31.0 ± 24,1; allergists: 115.9 ± 67.9; pulmonologists: blocks: 1) general aspects of inhaled therapy in asthma, 2) 62,2 ± 73,3). selection of inhaled drugs, 3) pressurized metered-dose inha­ Globally, 63 panelists (30.1%) had published at least one lers and spacers, 4) dry-powder inhalers, 5) breath-actuated article about asthma in a journal, 90 (43.1%) had at least one inhalers, and 6) therapeutic adherence and educational aspects communication in a conference, and 208 (99.5%) had con­ (Tables 1–4). The questionnaire was submitted to 210 specia­ ducted training sessions on asthma in the preceding year. lists from 16 out of the 17 Spanish autonomous regions: 70 After the first round of evaluation, consensus was reached primary care physicians, 70 allergists, and 70 pulmonologists. on 35 out of the 52 statements (67.3%). Seventeen items on Only one panelist (an allergist) did not complete the question­ which there was no consensus were subjected to a second naire, therefore, this panelist was excluded from the analysis. round of evaluation and a consensus was reached on 2 of In a second phase, the scientific committee selected the them. Subsequently, after 2 rounds of evaluation, it was pos­ members of a panel of experts to evaluate the items of the sible to reach a consensus on 37 out of the 52 proposed questionnaire. The panelists were selected according to their statements (71.1%) (Tables 1–4). experience and degree of knowledge or involvement in asthma. In the post hoc analysis of the results, for 14 out of the 52 The inclusion criteria for the selection of the panel of experts statements evaluated (26.9%) there was divergence among were the following: (1) more than 10 years of experience mana­ specialties when reaching an agreement. In other words, con­ ging asthma patients, (2) more than 50 follow-up consultations sensus was reached by one specialty but not by the others of asthma patients per month (more than 25 in the case of during the 1st or 2nd round of voting. These divergences are primary care physicians), (3) at least one asthma shown in Table 5. Table 1. Statements about general aspects of inhaled therapy in asthma and selection of inhaled drugs. Median Percentage of panelists in the median (IQR) region* Results Block I. General aspects of inhaled therapy (1) In terms of clinical effectiveness, the inhaled device is more important than the active drug (s) included within the different therapeutic 6 (3–7) 31.6% No consensus groups (e.g., LABA, ICS, etc.). (2)In a patient with a good inhaler technique, the particle size determines the lung deposition. 8 (7–9) 88.5% Agreement in 1st round (3)In the asthmatic patient, there are no clinically significant efficacy differences when using inhalers that generate fine or extra-fine particles. 4 (3–7) 22.0% No consensus (4)A high lung deposition rate is the one that reaches at least 40% of the metered dose. 7 (7–8) 77.5% Agreement in 1st round (5)More than half of primary care physicians have inadequate knowledge in the inhaler technique of the inhalers they prescribe. 7 (6–9) 69.9% Agreement in 1st round (6)More than half of specialized physicians have inadequate knowledge in the inhaler technique of the inhalers they prescribe. 7 (3–8) 54.1% No consensus (7)Critical errors in the handling of inhaled devices associated with poor control and/or the presence of exacerbations are common amongst 8 (7–9) 90.0% Agreement in 1st patients. round The most common cause of poor asthma control is: (8)Inadequate inhaler technique. 7 (5.5–8) 65.6% No consensus (9)Poor therapeutic adherence. 8 (7–9) 90.0% Agreement in 1st round When deciding on which type of inhaler to prescribe, it is necessary to consider: (10)The level of severity of asthma. 8 (6–9) 72.2% Agreement in 1st round (11)The patient’s degree of cognitive impairment. 9 (8–9) 92.8% Agreement in 1st round (12)The patient’s social support. 8 (7–9) 78.5% Agreement in 1st round Block II. Selection of inhaled drugs The most recommended treatment for intermittent asthma in adults and adolescents is: (13)PRN low-dose ICS/formoterol. 7 (4–8) 62.7% No consensus (14)PRN low-dose ICS/salbutamol. 3 (2–7) 52.2% No consensus (15)PRN SABA monotherapy. 4 (2–7) 18.2% No consensus The most recommended maintenance treatment for mild persistent asthma in adults and adolescents is: (16)Daily low-dose ICS 7 (5–8) 68.4% Agreement in 1st round (17)PRN low-dose ICS/formoterol. 7 (3–8) 53.1% No consensus (18)The most recommended salvage treatment for moderate persistent asthma in adults and adolescents is MART 8 (7–9) 85.6% Agreement in 1st round (19)In a controlled patient, it is necessary to wait for 3 to 6 months before stepping down therapy. 8 (7–9) 82.3% Agreement in 1st round (20)In an uncontrolled patient, the patient’s inhaler technique is usually checked before stepping up therapy. 9 (8–9) 85.6% Agreement in 1st round *It indicates the percentage of panelists who voted in the region where the median is (1–3; 4–6; 7–9). EXPERT REVIEW OF RESPIRATORY MEDICINE ICS: Inhaled Corticosteroid; IQR: Interquartile Range; LABA: Long-Acting β2 Agonists; MART: Maintenance and Reliever Therapy; PRN: as needed; SABA: Short-Acting β2 Agonists. 427 428 A. L. VALERO ET AL. 4. Discussion be prescribed. Probably, devices that omit the need for patient coordination between inhalation and actuation, may be parti­ In this multidisciplinary consensus, carried out using cularly useful for those patients with cognitive impairment a modified Delphi technique, a large group of experts from [19]. In addition, the panel members agreed that when decid­ primary care, allergy and pulmonology reached consensus on ing on which type of inhaler to prescribe, it is necessary to numerous issues related to inhaled therapy and management consider the patient’s social support. By social support, we of patients with asthma. mean that patients have family or close friends or providers Regarding general aspects of inhaled therapy (Table 1), the who can provide practical support and helps patients cope panel members agreed that critical errors in the handling of better with the medication administration. inhaled devices are frequent among the patients, and under­ Considering the selection of inhaled drugs (Table 1), the lined poor adherence as a major factor related to poor control. questionnaire tried to settle some controversies in the treat­ Critical errors are associated with uncontrolled asthma and/ ment of intermittent and mild persistent asthma [20]. These or increased rates of exacerbations [5]. Although poor inhaler are the two types of asthma that affect the majority of patients technique is an integral component of adherence, the scien­ and are predominantly attended by primary care physicians. tific committee differentiated these two concepts in the ques­ The use of short-acting ß2-agonists (SABA) in intermittent tionnaire (items 8 and 9) considering adherence as the extent asthma is open to debate. All guidelines and most physicians to which a patient follows the prescribed interval and dosing usually recommend salvage therapy with SABAs as needed regimen. These two factors, inhaler mishandling and poor (PRN) [6–9,20]. However, the primary pathogenic mechanism adherence, are common causes of poor disease control in of asthma is inflammation and SABAs neither treat inflamma­ many studies [12–15] and may undermine all the efforts tion nor reduce the risk of exacerbations [20]. Some authors made in the development of new inhaled drugs or in the argue that adding an inhaled corticosteroid (ICS) PRN in all rigorous updating of guidelines. Furthermore, a large part of patients with intermittent asthma may help to relieve symp­ the panel believed that many prescribers do not have ade­ toms and reduce the frequency of exercise-induced bronchial quate knowledge in the inhaler technique. This perception is constriction, as well as the risk of serious exacerbations and in line with a recent systematic review that evaluated the subsequent decline in lung function [4,20]. Based on indirect inhaler technique knowledge of health care professionals evidence, the 2019 Global Initiative for Asthma (GINA) guide­ (HCP) [5]. This review included data from 55 studies involving lines now recommend low-dose ICS/formoterol PRN as pre­ 6,304 HCPs who performed nearly 10,000 tests to demonstrate ferred controller in step 1 in adults and adolescents. This their inhaler technique proficiency. Overall, the inhaler techni­ combination is also one of the preferred options in step 2 que was considered correct in only 15.5% of the cases. together with daily low-dose ICS plus PRN SABA. In this regard, Surprisingly, the proficiency decreased over time from 20.5%, our panelists agreed on considering daily low-dose ICS as the in studies conducted from 1975 to1995, to 10.8% in studies preferred maintenance treatment for mild persistent asthma in conducted from 1996 to 2014. Our panelists’ opinion and adults and adolescents. However, they did not reach an agree­ these results highlight the urgent need to design efficient ment on the most recommended treatment for intermittent strategies to improve the training of HCP in the appropriate asthma (statements 13–15). Nevertheless, it is noteworthy that use of inhalers or the development of more user friendly treatment with low-dose ICS/formoterol PRN (statement 13) inhalers. was by far the panelists’ preferred option over other options Considering the size of the particles, the experts considered (low-dose ICS/salbutamol PRN or monotherapy with SABA that in a patient with a good inhaler technique, the size of the PRN), but it did not reach consensus by a narrow margin. In particles determines the lung deposition. The size of the par­ fact, in the post hoc analysis (Table 5), we observed that ticles is indeed an important factor in pulmonary deposition, pulmonologists reached an agreement in the 2nd round and although there are many other factors such as the plume considered low-dose ICS/formoterol PRN as the most recom­ speed, the airways geometry, the degree of humidity, the mended treatment for intermittent asthma in adults and ado­ mechanisms of clearance of the respiratory tract, etc [16]. lescents. So it is possible that this treatment option will Our panelists considered that a high pulmonary deposition become more commonly used in the future for this rate is the one that reaches at least 40% of the measured dose. population. This percentage is important since there are studies indicating that with the classic pressurized metered dose inhaler (pMDI) Another controversial issue concerns the best salvage treat­ only 9–10% of the administered drug particles reach the bron­ ment option for moderate persistent asthma since the guide­ chial tree, mainly due to two factors: the particles velocity is lines include the use of SABA or the use of the maintenance too high in pMDI, and the turbulent flow may favor deposition and reliever therapy (MART), which is the use of low-dose ICS/ in the oropharynx [17]. The use of the so-called ‘extrafine’ formoterol for both maintenance and salvage therapy [7,8,21]. aerosols could increase pulmonary deposition [18] but the Various studies suggest that MART may be associated with panel did not reach a consensus on the clinical importance a reduction in asthma exacerbations, despite requiring a lower of the use of inhalers that generate fine or extrafine particles. amount of ICS in both adults and adolescents [22–30]. In line The statement with the highest score, in the section about with this evidence, most panelists overwhelmingly consider general aspects of inhaled therapy, is the one considering the that the most recommended rescue treatment for moderate importance of taking into account patients’ degree of cogni­ persistent asthma in adults and adolescents is MART (state­ tive impairment when choosing which type of inhaler should ment 18). Table 2. Statements about pressurized metered-dose inhalers and spacers, and about dry-powder inhalers. Median Percentage of panelists in the (IQR) median region* Results Block III. Pressurized metered dose inhalers and spacers (21)The most frequent critical error of patients on pMDI treatment is the lack of coordination between actuation and inhalation. 9 (8–9) 99.0% Agreement in 1st round (22)In pMDI, slower plume speed implies less oropharyngeal deposition. 7 (6–8) 68.4% Agreement in 1st round (23)In acute asthma exacerbations attended in Primary Care, the use of pMDI with spacers is preferred to the use of nebulizers for the administration 8 (5–9) 68.4% Agreement in 1st of short-acting bronchodilators. round (24)In acute asthma exacerbations attended in a hospital setting, the use of pMDI with spacers is preferred to the use of nebulizers for the 7 (3–8) 55.5% No consensus administration of short-acting bronchodilators. (25)In your specialty consultations, the spacer is prescribed for more than 30% of patients on maintenance treatment with pMDI. 7 (3–8) 56.0% No consensus (26)It is recommended to use spacers when pMDI are prescribed as maintenance treatment for elderly patients 9 (8–9) 89.0% Agreement in 1st round When a patient performs the inhaler technique with a pMDI poorly, the most common approach is: (27)To switch to a non-pMDI device. 7 (4–8) 59.3% No consensus (28)To add a spacer to the pMDI. 8 (7–9) 81.3% Agreement in 1st round Block IV. Dry-powder inhalers (29)The most frequent critical error of the patients on treatment with DPI is not to perform a forceful inhalation. 8 (7–9) 83.7% Agreement in 1st round (30)Before prescribing a DPI, the ability of the patient to inhale forcefully is not checked. 7 (3,5–8) 62.2% No consensus (31)DPI requires a higher inspiratory flow than pMDI and BAI. 9 (8–9) 94.3% Agreement in 1st round (32)DPI produces more oropharyngeal side effects than pMDI and BAI. 7 (6–8) 67.5% Agreement in 1st round When a patient performs the inhaler technique with a DPI poorly, the most common approach is: (33)To switch to another DPI. 4 (2–7) 15.3% No consensus (34)To switch to a of non-DPI device 7 (6–8) 71.3% Agreement in 1st round * It indicates the percentage of panelists who voted in the region where the median is (1–3; 4–6; 7–9). BAI: Breath-Actuated Inhaler; DPI: Dry-Powder Inhaler; IQR: Interquartile Range; pMDI: pressurized Metered-Dose Inhaler. EXPERT REVIEW OF RESPIRATORY MEDICINE 429 430 A. L. VALERO ET AL. Table 3. Statements about breath-actuated inhalers. Table 4. Statements about therapeutic adherence and educational aspects. Percentage of Percentage of Median panelists in the Median panelists in the (IQR) median region* Results (IQR) median region* Results Block V. Breath-actuated Block VI. Therapeutic adherence and educational aspects inhalers (43)Patients need to get 9 (8–9) 92.3% Agreement (35)The fact that the BAI 9 (8–9) 98.6% Agreement involved in the choice of in 1st require neither in 1st inhaler device. round coordination, nor a forceful round inhalation, makes them (44)The ease of use of inhaler 8 (7–9) 85.2% Agreement devices is the most in 1st a suitable option for all important factor in round those patients with the promoting therapeutic ability to inhale voluntarily. adherence. (36)It is easier to train patients 9 (8–9) 92.3% Agreement to use BAI than pMDI. in 1st (45)The instructions on how to 7 (6–8) 71.3% Agreement use the inhaler in the in 1st round package leaflets are difficult round (37)It is easier to train patients 8 (6–9) 74.6% Agreement to use BAI than DPI. in 1st for patients to read and round understand. (38)It is easier for patients to 9 (8–9) 95.7% Agreement (46)In check-up visits it is 7 (6–8) 69.4% Agreement use a BAI than a pMDI. in 1st common that the inhaler in 1st round technique is NOT checked round (39)It is easier for patients to 8 (7–9) 80.4% Agreement periodically. use a BAI than a DPI. in 1st round (47)In check-up visits, 9 (8–9) 98.1% Agreement (40)To activate the BAI, only 8 (8–9) 94.3% Agreement a reevaluation of the inhaler in 1st minimal inspiratory effort is in 1st technique should be carried round required. round out. (41)The low error rate observed 8 (8–9) 94.3% Agreement (48)In check-up visits, 9 (8–9) 92.3% Agreement with BAI devices helps to in 1st adherence must be verified in 1st improve asthma control. round with a validated method. round (42)The low error rate observed 8 (7–9) 81.3% Agreement (49)In check-up visits, 6 (3–8) 17.7% No with BAI helps to reduce the in 1st therapeutic adherence is consensus overall cost of treatment round verified with a validated (healthcare and non- method before stepping-up healthcare related costs). therapies. (50)In check-up visits, the 7 (3–8) 53.6% No * It indicates the percentage of panelists who voted in the region where the patient is given a written consensus median is (1–3; 4–6; 7–9). BAI: Breath-Actuated Inhaler; DPI: Dry-Powder Action Plan. Inhaler; IQR: Interquartile range; pMDI: Pressurized Metered Dose Inhalers. (51)Nursing professionals are 8 (7–9) 76.6% Agreement capable to assess in 2nd therapeutic adherence and round correct errors of the inhaler technique. In the section centered in pMDI (Table 2), the panelists agreed on some weaknesses of these devices. The panelists (52)The use of software 7 (6–8) 70,8% Agreement applications helps to in 2nd considered that the most frequent critical error of patients on improve adherence to round pMDI treatment is the lack of coordination between actuation treatment and control of and inhalation (statement 21). In fact, this item reached the the disease. highest degree of consensus of the entire questionnaire and is * It indicates the percentage of panelists who voted in the region where the in line with the results of many studies [12–15]. To solve this median is (1–3; 4–6; 7–9). IQR: Interquartile range. problem, there was agreement on the option of incorporating a spacer (statement 28), especially in emergencies in the out­ patient setting (statement 23) and for the elderly (statement 26). However, the use of the spacer does not seem to happen a spacer. However, in the post hoc analysis, allergists agreed in frequently either in the emergencies attended in the hospital, 2nd round on the option to switch to a non-pMDI device. where nebulizers are preferred (statement 24), or paradoxi­ Regarding the use of dry-powder inhalers (DPI) (Table 2), cally, in the follow-up visits of patients on maintenance treat­ the panelists agreed that the most frequent critical error of ment with pMDI (statement 25). The limited use of the spacers patients on treatment with DPI is failure to perform a forceful during consultations may be due to their disadvantages [31]. inhalation. Furthermore, they considered that the use of DPI They are not very manageable and transportable due to their requires a higher inspiratory flow and produces more orophar­ large size, there are incompatibilities between the spacers yngeal side effects than pMDI and breath-actuated inhalers holes and the different models of pMDI in the market, they (BAI) (statements 29, 31, and 32). Inspiratory flow required for may reduce the perception of inhalation, or, in Spain, some most DPI ranges between 30 and 60 l/min, which is higher are not financed [32]. Additionally, it is noteworthy that, when than the necessary for a pMDI [33]. This fact can make their a patient performs the inhaler technique poorly with a pMDI, use by patients who are not capable of generating these flows the most common approach slightly differs among specialties difficult, such as elderly, people with severe bronchial obstruc­ because, globally, the best options seem to be the addition of tion or young children. Evidence shows that up to 32–38% of Table 5. Discrepancies in the consensus among specialties in the post hoc analysis. Statements Global* Primary care physicians Allergists Pulmonologists Block I. General aspects of inhaled therapy 5. More than half of primary care physicians have inadequate knowledge in the inhaler technique of the inhalers they prescribe. AG 1st R NC 1st R NC 1st R AG 1st R 8. The most common cause of poor asthma control is: Inadequate inhaler technique. NC 1st R AG 1st R NC 1st R NC 1st R NC 2nd R AG 2nd R NC 2nd R NC 2nd R 10. When deciding on which type of inhaler to prescribe, it is necessary to consider: The level of severity of asthma. AG 1st R AG 1st R AG 1st R NC 1st R Block II. Selection of inhaled drugs 13. The most recommended treatment for intermittent asthma in adults and adolescents is: PRN low-dose ICS/formoterol. NC 1st R NC 1st R NC 1st R NC 1st R NC 2nd R NC 2nd R NC 2nd R AG 2nd R 16. The most recommended maintenance treatment for mild persistent asthma in adults and adolescents is: Daily low-dose ICS AG 1st R AG 1st R NC 1st R AG 1st R Block III. Pressurized metered dose inhalers and spacers 22. In pMDI, slower plume speed implies less oropharyngeal deposition. AG 1st R NC 1st R AG 1st R AG 1st R 25. In your specialty consultations, the spacer is prescribed for more than 30% of patients on maintenance treatment with pMDI. NC 1st R NC 1st R NC 1st R NC 1st R NC 2nd R NC 2nd R NC 2nd R AG 2nd R 27. When a patient performs the inhaler technique with a pMDI poorly, the most common approach is: To switch to a non-pMDI device. NC 1st R NC 1st R NC 1st R NC 1st R NC 2nd R NC 2nd R AG 2nd R NC 2nd R Block IV. Dry-powder inhalers 30. Before prescribing a DPI, the ability of the patient to inhale forcefully is not checked. NC 1st R AG 1st R NC 1st R NC 1st R NC 2nd R AG 2nd R NC 2nd R NC 2nd R 32. DPI produces more oropharyngeal side effects than pMDI and BAI. AG 1st R AG 1st R NC 1st R AG 1st R 34. When a patient performs the inhaler technique with a DPI poorly, the most common approach is: To switch to a non-DPI device. AG 1st R AG 1st R NC 1st R AG 1st R Block VI. Therapeutic adherence and educational aspects. 45. The instructions on how to use the inhaler in the package leaflets are difficult for patients to read and understand. AG 1st R AG 1st R NC 1st R AG 1st R 46. In check-up visits it is common that the inhaler technique is NOT checked periodically. AG 1st R AG 1st R AG 1st R NC 1st R 50. In check-up visits, the patient is given a written Action Plan. NC 1st R NC 1st R AG 1st R NC 1st R NC 2nd R NC 2nd R AG 2nd R NC 2nd R *Statements agreed on 1st round were not submitted to a 2nd round of voting. AG: Agreement; NC: No Consensus; 1st R: first round of voting; 2nd R: second round of voting. BAI: Breath-Actuated Inhaler; DPI: Dry-Powder Inhaler; ICS: Inhaled Corticosteroid; pMDI: Pressurized Metered Dose Inhaler; PRN: as needed. EXPERT REVIEW OF RESPIRATORY MEDICINE 431 432 A. L. VALERO ET AL. patients on DPI treatment may perform insufficient inspiratory Limitations of this study include those inherent to a Delphi effort when using this type of device, and this error is asso­ consensus, mainly the inability to include the panelists’ opi­ ciated with poor asthma control and a higher rate of exacer­ nions or more details into the proposed statements. The pane­ bations [34]. In addition, DPI produce higher oropharyngeal list selection may be another limitation of the methodology impact than other devices [17], which would explain why the although we consider that the expertise of the panelists is panelists agreed that DPI produces more oropharyngeal side contrasted given the strict criteria used to select the panel. effects than pMDI and BAI. Possible influence of the scientific committee on the consen­ The last type of device evaluated by the panel was the sus is limited since they did not participate in the voting. breath-actuated inhaler (BAI) one (Table 3). The panelist agreed on the eight statements related to this device with no discordances between specialties. Panelists considered 5. Conclusions the BAI a suitable option for all those patients with the This multidisciplinary consensus brings together the opinion ability to inhale voluntarily, because they require neither of a large number of specialists with vast experience in asthma coordination nor a vigorous inhalation (statement 35). The management. This multidisciplinary group of experts primary focus on the BAI development was indeed to over­ endorsed the main recommendations on education and come the disadvantage of pMDI, namely the lack of coordi­ adherence proposed by national and international clinical nation and the inability of patients to synchronize actuation practice guidelines. However, the panelists did not fully with inhalation [35]. Additionally, these devices require agree on recent GINA recommendations about the treatment a minimum activation flow (30 l/min), which means that of the initial steps of the disease (intermittent and mild per­ 99% of patients can activate them on their first attempt, sistent asthma) regarding the PRN use of low-dose ICS/formo­ regardless of their forced expiratory volume in the terol combination as the preferred option. The experts valued first second (FEV1) or age [36]. Furthermore, evidence sug­ very positively the diverse characteristics of BAI and their gests that almost all patients can be trained quickly to use advantages over other inhaler devices. These agreements BAI, with 93% of them being capable of using the device might be taken into consideration for the next version of the correctly after 1 or 2 attempts [36]. In line with these find­ Spanish Asthma Guidelines (GEMA). ings, the panelists considered that it is easier to use BAI than pMDI or DPI and, moreover, it is easier to train patients to use the BAI than the pMDI or the DPI (statements 36–39). Acknowledgments The panelists also considered that the low error rate Writing and editorial assistance was provided by Dr. Pablo Rivas on behalf observed with the BAI might help to improve asthma con­ of Content Ed Net. Authors are grateful to all the participating panelists, trol and reduce the overall cost of treatment, although who voted the statements following the Delphi methodology: these statements would need to be verified in clinical Allergists: Alicia Alonso Gómez, Marta Alvariño Martín, José Amat López, María Teresa Audicana Berasategui, María Basagaña Torrento, studies. Diego Blanco García-Granero, Begoña Blanco Reinosa, Irina Diana Regarding the last section about therapeutic adherence Bobolea, Vicente Juan Cantó Reig, Francisco Carballada González, José and educational aspects (Table 4), the panelists agreed on Vicente Castello Carrascosa, José Ángel Cumplido Bonny, Consolación de Frutos Moreno, Carmen Díaz Donado, Miguel Ángel Díaz Palacios, various statements that can be considered as opportunities Carolina Escobar Bolaños, Salvador Fernández Meléndez, Ana Ferrer for improvement in the management of asthma patients Franco, Fernando Florido López, Juan Fraj Lázaro, Rocío Gámez and are in line with the current guideline recommenda­ Martín, Fernando García González, Ismael García Moguel, Aída Gómez tions [7–9]. During checkups, it would be advisable to Cardeñosa, David González de Olano, Isabel González Martín, Diego reevaluate the inhaler technique and check adherence Gutiérrez Fernández, Simoneta Hernández Reyes, Juan Manuel Igea Aznar, Francisco Javier Iglesias Souto, Pilar Alba Jordá, Gemma Jorro with a validated method. Furthermore, it would be neces­ Martínez, Natividad Labarta Sánchez, Antonio Letrán Camacho, Rafael sary to involve patients in the choice of the inhaler device Llatser Oliva, Ramón Lleonart Bellfill, Karen Milena Lozano Mosquera, and to simplify the instructions contained in the package Olga Luengo Sánchez, Teresa Macías Murelaga, Lluís Marqués Amat, leaflets. Finally, the experts valued the easiness of using Estefanía Moreno Mata, Elena Mederos Luis, Paula Méndez Brea, Juan inhaler devices as the most important factor to promote Carlos Miralles López, Ester Mohedano Vicente, Javier Montoro Lacomba, Ángel Javier Moral de Gregorio, Eva Morchón Miguel, therapeutic adherence, and supported the role of nursing Francisco Moreno Benítez, José Antonio Navarro Echeverría, Ana professionals and the use of new technologies, such as Navarro Pulido, Ramón Núñez Orjales, Luis Palacios Colom, Beatriz software applications, to improve adherence and disease Pola Bibian, Sergio Porcel Carreño, Patricia Prieto Montaño, Marta control. Reche Frutos, Manuel Jorge Rial Pardo, Ramón Rodríguez Pacheco, Interestingly, in the post hoc analysis, the divergence Mercedes Rodríguez Rodríguez, Ana Rosado Ingelmo, Francisco Ruano Pérez, Alejandro Sánchez Alonso, Inmaculada María Sánchez-Guerrero among specialties when reaching an agreement is not very Villajos, Pilar Serrano Delgado, Ana Tabar Purroy, Sonia Vázquez Cortés, high (14 out of the 52 statements evaluated). Taking into José María Vega Chicote, Sandra Vicario. account the differences between specialists (allergists and Primary care physicians: José Alfredo Agullo, Juan Luis Alonso Jerez, pulmonologists) and primary care, only in three statements Silvia Álvarez Álvarez, José Miguel Álvarez Cabo, José Antonio Álvaro (items 8, 22 and 30) primary care doctors’ opinions differ from Espinosa, Rubén Arandiga Caldes, Luis José Ignacio Buendía Fernández, Pilar Cajaraville Aso, Victoriano Chavero Carrasco, Ana Cieza Rivera, Juan specialists’ opinions (Table 5). This finding suggests that the Enrique Cimas Hernando, Carolina Cueca Valero, Susana Daviña Romero, primary care doctors, who were very carefully selected, are real Carmen de Luis Martín, José Ramón Fernández Fonfría, María Dolores asthma experts and their opinion is valuable. Fernández Ortega, Araceli Fernández Revuelta, Xavier Flor Escriche, Ana EXPERT REVIEW OF RESPIRATORY MEDICINE 433 Franco Alonso, Daniel García Avalos, César Sisto García de la Vega, José Declaration of interest Ignacio García García, María Luisa García Marqués, Marina García Pardo, Leovigildo Ginel Mendoza, Silvia González Carranza, Inmaculada González A Valero in the last five years received honoraria for speaking at spon­ García, Roberto Gorgues Comas, Antonio Hermoso Sabio, José Luis sored meetings from Astrazeneca, Boehringer Ingelheim, Chiesi. Act as Hernández García, Antonio Hidalgo Requena, José Antonio Ibáñez a consultant for ALK, Allergy Therapeutics, Leti, Astrazeneca, Novartis, Atienza, Francisco Emilio Juan Alcaraz, Luis Lample Lacasa, Armando Boehringer, Mundipharma, Mylan and Sanofi. And received funding/ Larnia Sánchez, María López Pérez, Liliana Raquel Losada Cucco, Emili grant support for research projects from Novartis, Astrazeneca, GSK, Marco Segarra, Mayte Marín Becerra, Sonia Martín Almendros, Yolanda Uriach, Leti, Sanofi and Menarini. J Trigueros in the last three years Martín Blázquez, José Martín Clos, Pedro Martín Pérez, Salvador Martínez received honoraria for speaking at sponsored meeting from Parra, Leandro Mena Roy, Jesús Méndez Cabeza, Virginia María Mirabal Astrazeneca, Boehringer Ingelheim, Chiesi, GSK, Mundipharma and Sánchez, Alberto Muguruza Valdeolmillos, Diego Murillo García, José Teva. Act as consultant for GSK, Novartis and TEVA. And received fund­ María Narváez Martín, Sara Núñez Palomo, Antonio Ortega Cabezas, ing/grant support for reseach project from Astrazeneca, Novartis and Miren Itxaso Orue Rivero, Jesús Pujol Salud, Ángel Puñal Pérez, Ramón Rovi Lab. V Plaza in the last three years received honoraria for speaking Quintana Díaz, Tomás Remesal Barranchina, Montserrat Rivera Teijido, at sponsored meetings from Astrazeneca, Boehringer Ingelheim, MSD Francisco Martín Ruiz Lavela, Ramón Ruiz Sales, Alfonso Sánchez and Chiesi. Received help assistance to meeting travel from Escudero, Juan Jesús Sánchez Pardo, Francisco Sarmiento Jiménez, Astrazeneca, Chiesi and Novartis. Act as a consultant for ALK, Mariona Serra Peralta, Pere Simonet Aneto, Tomás Soler López, José Astrazeneca, Boehringer Ingelheim, MSD, Mundipharma and Sanofi. Miguel Valero Pérez, Nancy Leonor Vera Nieto, José Manuel Vidal And received funding/grant support for research projects from Ameijide, Nuria Viejo Pinero. a variety of Government agencies and not-for-profit foundations, as Pulmonologists: Beatriz Abascal Bolado, Michael Alwakyl Obah, well as AstraZeneca, Chiesi and Menarini. The authors have no other Rubén Andújar Espinosa, Wilson Elías Arbaje Ortega, Aurelio Arnedillo relevant affiliations or financial involvement with any organization or Muñoz, Jesús Arribas Barcelona, Juan Manuel Arriero Marín, Miguel entity with a financial interest in or financial conflict with the subject Barrueco Ferrero, Asier Bengoechea Calafell, Luis Borderias Clau, Juan matter or materials discussed in the manuscript. 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