Letter to the Editor
Strengths of breath-triggered inhalers in asthma management
M. Morais-Almeidaa,1,
, H. Pitéb,c,1, J. Cardosod,e, R. Costaf,g, C. Robalo Cordeiroh,i, E. Silvaj,k, A. Todo-Boml,i, C. Vicentem,n, J. Agostinho Marqueso,p
Corresponding author
a Allergy Center, CUF Descobertas Hospital, Lisboa, Portugal
b Allergy Center, CUF Descobertas Hospital and CUF Infante Santo Hospital, Lisboa, Portugal
c CEDOC (Chronic Diseases Research Center), NOVA Medical School, Lisboa, Portugal
d Pulmonology Department, Centro Hospitalar de Lisboa Central, Lisboa, Portugal
e NOVA Medical School, Lisboa, Portugal
f Family Medicine, Porto, Portugal
g Coordinator of GRESP (Grupo de Estudos de Doenças Respiratórias da APMGF), Portugal
h Pulmonology Department, Centro Hospitalar Universitário de Coimbra, Portugal
i Faculty of Medicine, University of Coimbra, Portugal
j Family Medicine USF João Semana, Ovar, Aveiro, Portugal
k Coordinator of GRESP Inhalers and Technical Devices Working Group, Portugal
l Immunoallergology Department, Centro Hospitalar Universitário de Coimbra, Portugal
m Family Medicine UCSP Soure, Coimbra, Portugal
n Secretary of GRESP (Grupo de Estudos de Doenças Respiratórias da APMGF), Portugal
o Pulmonology Department, Centro Hospitalar de São João, Porto, Portugal
p Faculty of Medicine, University of Porto, Portugal
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"apellidos" => "Agostinho Marques" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">o</span>" "identificador" => "aff0075" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">p</span>" "identificador" => "aff0080" ] ] ] ] "afiliaciones" => array:16 [ 0 => array:3 [ "entidad" => "Allergy Center, CUF Descobertas Hospital, Lisboa, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Allergy Center, CUF Descobertas Hospital and CUF Infante Santo Hospital, Lisboa, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "CEDOC (Chronic Diseases Research Center), NOVA Medical School, Lisboa, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Pulmonology Department, Centro Hospitalar de Lisboa Central, Lisboa, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "NOVA Medical School, Lisboa, Portugal" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Family Medicine, Porto, Portugal" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Coordinator of GRESP (Grupo de Estudos de Doenças Respiratórias da APMGF), Portugal" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Pulmonology Department, Centro Hospitalar Universitário de Coimbra, Portugal" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Faculty of Medicine, University of Coimbra, Portugal" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Family Medicine USF João Semana, Ovar, Aveiro, Portugal" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Coordinator of GRESP Inhalers and Technical Devices Working Group, Portugal" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Immunoallergology Department, Centro Hospitalar Universitário de Coimbra, Portugal" "etiqueta" => "l" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Family Medicine UCSP Soure, Coimbra, Portugal" "etiqueta" => "m" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Secretary of GRESP (Grupo de Estudos de Doenças Respiratórias da APMGF), Portugal" "etiqueta" => "n" "identificador" => "aff0070" ] 14 => array:3 [ "entidad" => "Pulmonology Department, Centro Hospitalar de São João, Porto, Portugal" "etiqueta" => "o" "identificador" => "aff0075" ] 15 => array:3 [ "entidad" => "Faculty of Medicine, University of Porto, Portugal" "etiqueta" => "p" "identificador" => "aff0080" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0010" class="elsevierStylePara elsevierViewall">Asthma affects the lives of several hundred million people around the World, across all age groups and Portugal is not an exception, with an asthma lifetime prevalence of 10.5%.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Patients, their families and the society face high direct and indirect costs, due to healthcare resources use, loss of productivity, absenteeism and presenteeism of patients. Asthma strongly influences the wellbeing and quality of life of patients. With no established curative treatment, guidelines for asthma management have identified that the primary goal of management is to achieve asthma control.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> In asthma, pharmacological treatments mainly consist of inhaled drugs, which allow efficacy and significantly reduce systemic side effects, being the most efficacious treatments. However, lack of adherence to treatment in asthma occurs in more than half of all medical prescriptions. Furthermore, reduced adherence to treatment frequently allies with an incorrect inhalation technique, both considered major issues significantly impairing pharmacologic treatments effectiveness. Therefore, despite the efficacy of the available drugs, a high percentage of asthmatics are uncontrolled and have frequent exacerbations.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Difficulties in using inhalation methods are well-known problems that have been consistently maintained in recent decades, with the occurrence of several errors that affect treatment results with the use of both dry powder inhalers (DPIs) and pressurized metered-dose inhalers (pMDIs). Results from the Critikal study<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> analyses of the inhaler technique assessment initiative Helping Asthma in Real-life Patients (iHARP) database have helped to identify the prevalence of critical inhaler errors (those that have a definite detrimental impact on the delivery of drug to the lungs) with different devices in patients with asthma. The most common critical errors included failure to coordinate device actuation and inhalation with pMDIs, and lack of a forceful inhalation with DPIs; overall, 89% of patients made at least one potentially critical handling error and 67% made multiple potentially critical errors.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Breath-actuated inhalers (BAIs) represented an evolution in inhalers’ design aiming to improve the management of asthma.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> BAIs are aerosol devices, like pMDIs, but rather than being activated manually, they automatically release a dose of drug when the patient inhales with a sufficient inhalation flow rate. In the past, BAIs had a major limitation when chlorofluorocarbon propellants (CFCs) were used and the speed of emission of the aerosol was so high that the impact of inhaled droplets in the upper airways was still very significant; nowadays, with hydrofluoroalkane propellants (HFAs), the speed of emission is considerably lower and the aerosol may be inhaled slowly being deposited more peripherally in the airways. These new devices may offer several advantages (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), and were developed to overcome the most commonly seen critical errors with other inhalers, as follows: there is no need to coordinate actuation and inhalation (which is necessary for pMDIs); as active devices, BAIs emit a propelled aerosol and patients do not need to inhale forcibly to generate respirable particles (which is required for DPIs).<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">4,5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">BAIs are intended to simplify the inhaler technique, leading to improved inhaler use by the patients and less health care professional (HCP) time spent training patients to use the devices correctly.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> Indeed, several studies have shown that patients find BAIs easier to use and HCP find it easier to train patients in their correct use in relation to other devices. The ease of use of BAIs may offer particular advantages in certain patient groups, such as children, the elderly or those with limited manual dexterity.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">4,5</span></a> BAIs that are triggered by a low inspiratory force may offer additional advantage.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">An ergonomically designed breath-triggered inhaler (BTI), k-haler®,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> was recently available. Its successful use involves only a few steps and, as an ‘active’ aerosol inhaler, it automatically releases a dose of the drug in a respirable form when a patient inhales, even at a low inspiratory flow (the device is triggered at an inspiratory flow rate of approximately 30<span class="elsevierStyleHsp" style=""></span>L/min). A high fine particle fraction and a plume that is less forceful than that of previous pMDIs can decrease drug impaction at the back of the throat and improve delivery to the lungs.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> As such, k-haler® represents an added-value to improve asthma control by addressing current patients’ needs and overcoming the most common lasting critical errors referred with other inhalers (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The simplicity of use, better inhaler handling and patient preference for BAIs are advantages that may translate into improved treatment compliance with the prescribed therapy, leading to improved lung function and asthma control compared with other devices.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">4–6</span></a> Several controlled studies comparing the efficacy of drugs at equivalent nominal doses administered with different devices had demonstrated equivalence in the main clinical outcomes (mostly symptoms and exacerbations) of asthma (or chronic obstructive pulmonary disease), but this may be justified by, 1. the large number of variables affecting the clinical response to inhaled drugs, besides the inhalation technique and 2. the gap between the patients in clinical trial conditions in referral centers with specific characteristics and close monitoring, being aware that they are being evaluated, and those patients in the real world, where poor inhalation technique and low adherence to therapy are known to be more common.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3–7</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">If correctly and effectively used, inhalers are excellent, safe and effective in controlling asthma, as in other chronic respiratory diseases.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> Improving inhalers correct and effective use is therefore a global issue to overcome current known difficulties and to move forward into achieving higher rates of asthma control.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical disclosures</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Protection of human and animal subjects</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this article.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Confidentiality of data</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Right to privacy and informed consent</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Funding</span><p id="par0060" class="elsevierStylePara elsevierViewall">None to declare.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">None to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0005" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Right to privacy and informed consent" ] ] ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">These authors should be considered co-first authors (equal contributions and credit to the work).</p>" "identificador" => "fn1" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Advantages \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Disadvantages \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Portable and compact• Multi-dose device• High reproducibility in the amount of drug delivered• Closed canister, so contents cannot be contaminated<span class="elsevierStyleItalic">Benefits over conventional pMDIs</span>– No need to coordinate inhalation and actuationBenefits over DPIs– Releases drug at low inspiratory force, so no need to inhale forcibly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Available for a limited range of drugs• Suspension formulations need to be shaken before each use• Important to prime before first use, if not used for some time or if the inhaler has been exposed to cold temperatures \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2370180.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Breath-actuated inhalers: key advantages and disadvantages.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">General design</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Minimal inhalation force is required to trigger the device \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Ensures that a dose is released even if the patient has limited lung capacity and gives a ‘nice feel’ upon actuation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Shape \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Retains the classic ‘pMDI’ shape familiar to patients; the size and shape of DPIs vary considerably, which can lead to patient confusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Orange translucent cap and silver detailing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Helps patients to orientate the inhaler correctly and to identify the mouthpiece correctly \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Small, compact size \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Easy to store and carry, and fits nicely in the hand (even small hands)• Can be used discreetly and has a comfortable fit in the mouth \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Closed system \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Prevents dirt and dust from accumulating in the inhaler that could clog the device and irritate patients’ airways \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Usability</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Open–breathe–close operation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Few simplified steps are required to prime and operate the device \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cap is connected to the device \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• The cap cannot be lost and can be repositioned easily when priming/closing \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Dose feedback</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Easy-to-read dose counter in font designed specifically by the UK Royal National Institute for the Blind \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Ensures that patients know how many doses are left \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Audible ‘clicks’ when dosing and when closing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Feedback that the device is primed and ready for use and also when the cap has been closed securely \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Automatic release of dose when the mouthpiece cap is closed if a primed dose is not taken \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">• Alerts the patient that a dose has not been taken• Prevents double or multiple-dosing \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2370181.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Key attributes of the breath-triggered k-haler®.</p>" ] ] ] 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| Year/Month | Html | Total | |
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| 2024 November | 14 | 4 | 18 |
| 2024 October | 91 | 37 | 128 |
| 2024 September | 79 | 34 | 113 |
| 2024 August | 78 | 35 | 113 |
| 2024 July | 75 | 31 | 106 |
| 2024 June | 67 | 25 | 92 |
| 2024 May | 44 | 39 | 83 |
| 2024 April | 49 | 35 | 84 |
| 2024 March | 67 | 26 | 93 |
| 2024 February | 33 | 20 | 53 |
| 2024 January | 39 | 21 | 60 |
| 2023 December | 23 | 23 | 46 |
| 2023 November | 56 | 62 | 118 |
| 2023 October | 68 | 43 | 111 |
| 2023 September | 41 | 30 | 71 |
| 2023 August | 34 | 16 | 50 |
| 2023 July | 60 | 34 | 94 |
| 2023 June | 73 | 19 | 92 |
| 2023 May | 70 | 39 | 109 |
| 2023 April | 48 | 19 | 67 |
| 2023 March | 81 | 25 | 106 |
| 2023 February | 70 | 34 | 104 |
| 2023 January | 29 | 21 | 50 |
| 2022 December | 84 | 24 | 108 |
| 2022 November | 60 | 41 | 101 |
| 2022 October | 78 | 39 | 117 |
| 2022 September | 35 | 42 | 77 |
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| 2022 July | 41 | 58 | 99 |
| 2022 June | 43 | 39 | 82 |
| 2022 May | 60 | 44 | 104 |
| 2022 April | 93 | 33 | 126 |
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| 2022 February | 90 | 36 | 126 |
| 2022 January | 74 | 53 | 127 |
| 2021 December | 51 | 41 | 92 |
| 2021 November | 61 | 40 | 101 |
| 2021 October | 57 | 61 | 118 |
| 2021 September | 56 | 41 | 97 |
| 2021 August | 47 | 35 | 82 |
| 2021 July | 37 | 29 | 66 |
| 2021 June | 47 | 31 | 78 |
| 2021 May | 48 | 46 | 94 |
| 2021 April | 135 | 92 | 227 |
| 2021 March | 48 | 41 | 89 |
| 2021 February | 44 | 37 | 81 |
| 2021 January | 45 | 33 | 78 |
| 2020 December | 32 | 26 | 58 |
| 2020 November | 67 | 25 | 92 |
| 2020 October | 99 | 50 | 149 |
| 2020 September | 219 | 84 | 303 |
| 2020 August | 104 | 38 | 142 |
| 2020 July | 94 | 34 | 128 |
| 2020 June | 75 | 33 | 108 |
| 2020 May | 15 | 8 | 23 |
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