key: cord-0025541-i0bexop1
authors: Ohar, Jill A; Ferguson, Gary T; Mahler, Donald A; Drummond, M Bradley; Dhand, Rajiv; Pleasants, Roy A; Anzueto, Antonio; Halpin, David M G; Price, David B; Drescher, Gail S; Hoy, Haley M; Haughney, John; Hess, Michael W; Usmani, Omar S
title: Measuring Peak Inspiratory Flow in Patients with Chronic Obstructive Pulmonary Disease
date: 2022-01-06
journal: Int J Chron Obstruct Pulmon Dis
DOI: 10.2147/copd.s319511
sha: ba51604ff75cd015962ca88fe708c220064755e4
doc_id: 25541
cord_uid: i0bexop1

Dry powder inhalers (DPIs) are breath actuated, and patients using DPIs need to generate an optimal inspiratory flow during the inhalation maneuver for effective drug delivery to the lungs. However, practical and standardized recommendations for measuring peak inspiratory flow (PIF)—a potential indicator for effective DPI use in chronic obstructive pulmonary disease (COPD)—are lacking. To evaluate recommended PIF assessment approaches, we reviewed the Instructions for Use of the In-Check™ DIAL and the prescribing information for eight DPIs approved for use in the treatment of COPD in the United States. To evaluate applied PIF assessment approaches, we conducted a PubMed search from inception to August 31, 2021, for reports of clinical and real-life studies where PIF was measured using the In-Check™ DIAL or through a DPI in patients with COPD. Evaluation of collective sources, including 47 applicable studies, showed that instructions related to the positioning of the patient with their DPI, instructions for exhalation before the inhalation maneuver, the inhalation maneuver itself, and post-inhalation breath-hold times varied, and in many instances, appeared vague and/or incomplete. We observed considerable variation in how PIF was measured in clinical and real-life studies, underscoring the need for a standardized method of PIF measurement. Standardization of technique will facilitate comparisons among studies. Based on these findings and our clinical and research experience, we propose specific recommendations for PIF measurement to standardize the process and better ensure accurate and reliable PIF values in clinical trials and in daily clinical practice.

Chronic obstructive pulmonary disease (COPD) is a lung condition associated with cough and breathlessness, which worsens over time. COPD treatment includes inhaled medicines that can be given using pressurized metered-dose inhalers (pMDIs) or by dry powder inhalers (DPIs). The basic difference between pMDIs and DPIs is how the medicine gets to the lungs. pMDIs use a propellant to deliver the medicine into the airways, while DPIs do not contain propellants. DPIs need considerable patient effort while breathing, and each DPI has different internal resistance and breathing method. Peak inspiratory flow (PIF) measures the maximum amount of air that can be inhaled during one deep breath and is an important measure of effective DPI use. Suboptimal PIF is common and occurs in the most vulnerable COPD patients. The In-Check™ DIAL measures PIF for DPIs. There is lack of guidance for measuring PIF; we reviewed the Instructions for Use of the In-Check™ DIAL, prescribing information for eight approved DPIs, and evidence from 47 studies.

Inhaled medications for chronic obstructive pulmonary disease (COPD) can be administered using a pressurized metered-dose inhaler (pMDI), soft-mist inhaler (SMI), nebulizer, or dry powder inhaler (DPI). 1 Each inhalation device is unique and has associated advantages and disadvantages. 2,3 pMDIs deliver a fixed drug dose as aerosol droplets from a pressurized canister and require coordination between inhalation and actuation, which can be challenging for some patients and may lead to reduced drug deposition in the lungs. 4 The SMI generates a slowmoving aerosol cloud from an aqueous drug solution using mechanical energy. The slow-moving aerosol provides more time for better inhalation-actuation coordination, which may enhance drug delivery. 5 However, some patients may find loading the cartridge into the inhaler challenging. 2 Nebulizers use an external power source to generate a continuous aerosol from a liquid drug formulation and require minimal coordination and effort during inhalation; however, most nebulizers are bulky, time consuming to use, and need cleaning after use. 6 Furthermore, the drug formulation (viscosity and surface tension) may influence aerosol production. 6 DPIs depend on the patient's inspiratory flow (IF) to deaggregate drug and carrier particles and to disperse and deliver the aerosolized drug into the lungs. 2, 4 Unlike pMDIs and SMIs, which have minimal internal resistance, each DPI has a unique internal resistance and requires unique inhalation maneuvers. 2, 3 Furthermore, patients may struggle to remember directions associated with different inhaler types. 7 DPIs are breath actuated and, unlike most pMDIs and the SMI, rely on the patient's IF through a resistor during the inhalation maneuver. 3 Peak inspiratory flow (PIF) is defined as the maximal airflow (liters per minute) achieved during a forced inspiratory maneuver. 8, 9 Patients' inspiratory effort depends on their respiratory muscle strength and the lung volume from which they initiate the inhalation (functional residual capacity [FRC] , residual volume [RV] , or somewhere in between). [10] [11] [12] The patient's inspiratory effort produces a pressure drop that determines the IF, depending on the inhaler's specific internal resistance. 11 Effective use of a DPI will depend on the patients' IF (optimal PIF is preferred) as well as the turbulence generated by the specific internal resistance of the DPI. 1,10 Sufficient effort, pressure drop, and consequent PIF are needed for effective release of the dry powder from the capsule, blister pack, or reservoir; disaggregation of drug-carrier agglomerates; and optimal dispersal and deposition of respirable drug particles (<5 μm in mass median aerodynamic diameter) into the lower airways. 8, 10, 11, 13 Other factors that affect optimal drug delivery with DPIs include incorrect inhaler preparation, 14 poor clinical status, 15 and-because of the powder formulation-a humid environment. 14, 16 Internal resistances vary substantially across DPIs; therefore, the degree of flow and force needed on behalf of the patient for effective drug dispersal and lung deposition also varies. 17 "Optimal" PIF is the IF needed to generate a high fine-particle fraction, which enables an adequate proportion of the total drug (fine particle [1-5 μm] dose) to be delivered throughout the lungs. 8, 10, 18 A PIF of <60 L/min is generally considered to be suboptimal (below the optimal threshold for the inhaler) for most DPIs; 3,9,10 however, "optimal" PIFs ranging from 30 to 65 L/min have been reported for different DPIs depending on each DPI's unique internal resistance. 19 A "suboptimal" PIF can result in inadequate drugcarrier disaggregation and insufficient drug deposition deep in the airways, 8 which can lead to side effects from oropharyngeal deposition. 19 In some studies, older age, 20 female sex, 8, 21 short stature, 20,21 and low forced vital capacity (FVC) 20, 21 and inspiratory capacity 20,21 were associated with low PIFs. However, other studies have not shown any association between age, 8, 22 sex, 22 height, 22, 23 or FVC 8, 20 and PIF. Inspiratory muscle weakness, hyperinflation, concurrent exacerbation, or cachexia may also decrease PIF. 15, [23] [24] [25] The patient's clinical status should be considered when measuring PIF 10 -if a minimal value is chosen when the patient is clinically stable, exacerbations may lead to a below minimally acceptable PIF.

Given that multiple patient and clinical factors can potentially impact PIF, direct measurement is necessary to confirm that patients are able to optimally use the selected DPI. 18 Although inhalation parameters can be measured using https://doi.org/10.2147/COPD.S319511

International Journal of Chronic Obstructive Pulmonary Disease 2022:17 80 spirometry, assessment of PIF using conventional spirometry does not account for the internal resistance of DPIs 26 and, thus, does not directly determine a patient's ability to generate the device-specific PIF required. 27 The In-Check™ DIAL inspiratory flow meter, however, is a device that can be used to assess PIF against the simulated internal resistance of a specific DPI: 28, 29 no (R0), low (R1), medium low (R2), medium (R3), medium high (R4), or high (R5) resistance 8 (Table 1 ; https://editage.sharefile.com/share/view/ s744a7fee41d149bf9f345fd8d59291a7). Results from measurements obtained using the device indicate whether a patient can achieve the optimal PIF for the selected DPI and can be helpful in guiding patients' inspiratory effort for the specific DPI. [29] [30] [31] However, all clinicians-especially those in developing countries-may not have access to the In-Check™ DIAL. 26 In addition to the In-Check™ DIAL, other measurement devices (attachments for DPIs or built-in devices) are in development or available to determine inhalation parameters through DPIs (Supplementary Methods). Alternatively, PIF can be measured using an inhalation profile recorder. [32] [33] [34] [35] PIF is a potential indicator for effective DPI use; 9 however, the approach for measuring PIF is not standardized. Therefore, an accurate assessment of the prevalence of suboptimal PIF and its impact on clinical outcomes cannot be ascertained. Variables in PIF assessment include the device used for assessment, instructions for exhalation before inhalation (eg, from RV; after forced expiration or slow exhalation vs FRC; after passive end-tidal expiration), number of resistance settings tested, physical position of the patient with the inhaler, and PIF calculation (one measurement vs average of multiple measurements vs best of multiple measurements). Notably, the intensity of inspiratory effort (eg, "sharp," "quick," "maximal," "forceful," and "full") differs based on patients' perceptions and varies for each inhaler according to the respective Instructions for Use. For example, a "sharp, maximal" effort will produce a different PIF versus a "full, deep" breath.

Herein, we describe findings from a systematic evaluation of recommended and applied PIF assessment approaches and, accordingly, propose a practical and standardized method of PIF measurement.

An international panel of experts was convened under the leadership of J.A.O., D.A.M., G.T.F., and O.S.U. We agreed that a standardized approach to measuring PIF in clinical trials and daily clinical practice was needed and posed the following three questions that needed to be addressed: (1) How should patients and the PIF assessment device be positioned during assessment?, (2) How should patients be instructed to exhale before assessment?, and (3) How should patients be instructed to inhale during assessment? We devised an approach to collect relevant information from published sources (Instructions for Use of In-Check™ DIALs and applicable DPIs, as well as 46 and Inhub ® (Mylan Pharmaceuticals Inc., Morgantown, WV, USA). 47 

To identify how PIF was measured in various clinical and real-life studies, we conducted a PubMed search from inception to August 31, 2021, using the following search string: ("Peak inspiratory flow" OR PIF) AND ("dry powder inhaler" OR DPI). Search results were imported into an EndNote (Clarivate Analytics, Philadelphia, PA, USA) library. Abstracts and full texts were reviewed and independently verified by all authors. Reports of PIF measurement in patients with COPD using DPIs were used in the analysis. In addition, authors contributed reports from their personal libraries that were not captured during the PubMed search as applicable.

We documented basic directions included in the Instructions for Use of the In-Check™ DIAL (Table 2) , daily use sections of the Instructions for Use of the eight DPIs approved by the FDA for use in COPD (Table 3) , and the methodology sections of published reports of studies where PIF was assessed among patients with COPD using DPIs (Supplementary Table 1 ), as well as the thresholds for optimal and/or suboptimal PIFs from published reports of studies and the mean PIF value measured, where available (Supplementary Table 2 ). Instructions on how to exhale before the inhalation maneuver, the inhalation maneuver itself, and post-inhalation breath-hold varied (Tables 2, 3, and Supplementary  Table 1 ). In many instances, instructions seemed vague and/or incomplete, and no clear guidance as to whether to measure PIF from RV or FRC was provided. Likewise, specific details regarding how PIF was measured in clinical and real-life studies were often vague, incomplete, or absent.

How to assess whether a patient can achieve PIF within the clinically effective range of a particular DPI is outlined in the Instructions for Use of the In-Check™ DIAL (Table 2) . 30, 36 A notable difference between the 2010 (In-Check™ DIAL) and 2016 (In-Check™ DIAL G16) versions of the device is the instruction recommended by the manufacturer to "exhale slowly and deeply" (2010) versus "exhale fully" (2016) before inhalation. No additional direction is provided in either instance; however, the instructions accompanying the In-Check™ G16 more closely mimic patient instructions for most DPIs. No instruction regarding the physical position of the patient's head or body or the inhaler/In-Check™ DIAL is provided in the Instructions for Use. However, a video demonstrating the use of the In-Check™ DIAL, which shows that the device should be held horizontally during PIF measurement after exhalation, is available on the manufacturer's website. 31 

Steps for daily use of the eight DPIs are summarized in Table 3 . [40] [41] [42] [43] [44] [45] [46] [47] Instructions for exhalation included "breathe out (exhale) as long as you can" (Diskus ® and Inhub ® ); 40,47 "breathe out (exhale) fully" (Ellipta ® and Neohaler ® ); 41,43 "breathe out completely in one breath, emptying your lungs of any air" (HandiHaler ® ); 42 "breathe out completely" (Pressair ® ); 44 and breathe out (exhale) through your mouth and push as much air from your lungs as you can (RespiClick ® and Digihaler™). 45, 46 Instructions for inhalation included "breathe in quickly and deeply" (Diskus ® , Inhub™, RespiClick ® , and Digihaler™); 40,45-47 "take a long, steady, deep breath" (Ellipta ® ); 41 "breathe in deeply until your lungs are full" (HandiHaler ® ); 42 deeply as you can" (Neohaler ® ); 43 and "take a strong, deep breath" (Pressair ® ). 44 Instructions for patients' head positioning were included for HandiHaler ® ("hold your head in an upright position while you are looking straight ahead") 42 and Pressair ® ("hold your head upright"). 44 Instructions for patients' body positioning were not included for any other DPI. Most Instructions for Use included the following statement: The actual amount of drug delivered to the lung will depend on patient factors, such as IF profile. [40] [41] [42] [43] [44] [45] [46] [47] Instructions for inhaler positioning were provided for all DPIs.

Of the 128 articles retrieved, 40 were reports of studies where PIF was measured through a DPI or using the In-Check™ DIAL in patients with COPD. 7, 8, 12, [20] [21] [22] [23] [24] 26, 32, 34, 35, Reports of asthma studies (n = 30); review articles (n = 10); and non-English language articles, editorials, and articles involving healthy subjects or patients with other respiratory diseases; or reports from modeling/simulations (n = 48) were excluded. An additional seven articles were included from the authors' personal libraries; 33,76-81 therefore, a total of 47 reports were included in the analysis.

PIF was measured using DPIs and/or inhalation profile recorders in 25 (53.2%) studies and the In-Check™ DIAL or other devices in the remaining 22 (46.8%) studies (Supplementary Table 1 ). In most published reports of studies where PIF was measured using the In-Check™ DIAL, thresholds for optimal and/or suboptimal PIF were reported (Supplementary Table 2) .

In a few studies, patients were reportedly seated during inhalation. 12, 22, 24, 52, 64, 72 The position of the inhaler was reported in three studies to be vertical (Pulvinal™ and Turbuhaler ® ) 62 or upright (NEXThaler 70 and Turbuhaler ®74 ). The position of the patient's head during inhalation was not reported in any study. Overall, the PIF measurement details, including inhalation instructions, were provided or participants were referred to patient information leaflets in 35 A gentle tap will dislodge the magnetic resetting weight, which will return the red cursor to a start position. When this has happened, the meter must turn through 180 degrees to return the magnetic weight to 

Prescribing Information)

Neohaler ® (indacaterol and glycopyrrolate) 43 

Ohar et al exhale," 62 "breathe out completely," 74 and "breathe out as far as comfortable". 70 In one study, PIF was measured after patients were asked to inhale as they normally do. 49 In four studies, patients were asked to inhale as they did at home with their own inhaler using the In-Check™ DIAL (with the resistance set to the specific inhaler they used), 8, 61, 74, 81 and in one of these four studies, patients judged to have a weak inhalation were instructed to inhale more forcefully before another PIF measurement was taken. 61 For most studies where the In-Check™ DIAL was used, resistance was set to match the internal airflow resistance of the respective inhaler(s). 8, 12, 20, 21, 23, 24, 55, 57, 58, 61, 63, 67, 74, 76, 80, 81 PIF calculation, however, varied across studies. In some studies, the highest PIF value of two 7, 49, 76 or three 12, [20] [21] [22] [23] [24] [33] [34] [35] 48, 56, 57, 59, 63, 67, 72, 74, 75, 80 replicate inhalations per inhaler was used for analyses; in two studies, average values were reported. 8, 55 In other studies, the patient performed inhalation maneuvers until two consecutive PIF readings were within 20% of each other. 26, 66 

The ability to generate an optimal IF is essential for effective aerosol drug delivery from a DPI. 8, 18 Therefore, standardization of PIF measurements is critical to making uniform decisions in clinical practice. In this systematic evaluation of recommended and applied PIF assessment approaches, we observed considerable variations in the way patients were instructed to use their inhalers, as well as how PIF was measured in clinical and real-life studies.

First, the Instructions for Use for the In-Check™ DIAL lacked specific guidance regarding the positioning of the patient's head and body or inhaler. Likewise, steps for daily use of the eight analyzed DPIs varied in many respects and lacked in-depth instruction. Furthermore, instructions provided to patients during PIF assessments in clinical and real-life studies were diverse and often vague. In a few studies, instructions were in line with patient information leaflets/Instructions for Use brochures. 7, 51, 53, 56, 59, 62, 68, 71, 72, 74 In other studies, the instructions were not consistent with the Instructions for Use leaflet for the DPI being evaluated. 76, 79 The contents of the Instructions for Use of the In-Check™ DIAL were consistent with instructions provided to patients using DPIs in one study 58 but not in others. 21, 23 In clinical studies, patients were often provided rather straightforward, but inconsistent, instructions for the inhalation maneuver; however, they were seldom clearly instructed on how to exhale beforehand. Therefore, patients were not optimally preparing for the PIF assessment.

Factors such as the position of the patient's head such that the chin is slightly upward affect drug deposition and, subsequently, outcomes in asthma. 82 The effect of posture on aerosol delivery from DPIs has not been reported. However, in a study evaluating regional lung deposition using a nebulized drug (median mass aerodynamic diameter of 4.9 µm), aerosol delivery was shifted to the bronchial airways rather than the alveolar region when the drug was administered in the supine versus seated position. 83 Differences in FRC and regional changes in ventilation accounted for these findings. We recommend that patients maintain an upright seated or erect standing position-with the chin pointed slightly upward-during the PIF assessment process. In the Instructions for Use of the In-Check™ DIAL and DPIs and in clinical and real-life studies, the definition of "full exhalation" varied. In a large observational prospective study, the ability of patients with COPD to breathe out completely in one breath was reported to be one of the most problematic steps with inhaled medication use. 84 Although exhaling completely is recommended in the Instructions for Use for most DPIs, expert opinion suggests that patients who exhale "fully and completely" (down to RV) could collapse their small airways at very low lung volumes. There are, however, no published data that support this widely held opinion other than the textbook by Bouhuys that notes that breathing at low lung volumes for prolonged periods results in atelectasis. 85 Therefore, during the subsequent inhalation phase, the "energy" generated by the inhaled breath/volume must overcome the "opening" of the collapsed small airways caused by exhaling "fully and completely." The resultant energy available during inhalation to overcome airway collapse may be (not yet proven) inadequate to generate the required inspiratory acceleration and energy necessary to optimally activate the DPI. Although RV is a desirable measurement point, it is often difficult to assess and obtain. Furthermore, patients who are hospitalized or frequently ill are unable to exhale to RV. Therefore, considering these variabilities and potential challenges with complete exhalation, we recommend "breathing out slowly and fully," which is generally consistent with the Instructions for Use for DPIs and can be realistically performed by a patient in a clinical setting.

Although patients were generally provided with the actual direction about the inhalation maneuver in clinical studies, instructions varied. Patients were instructed to breathe in "rapidly/forcefully and deeply" in some studies, 57, 62, 70, 74, 79 but in others, they were told to take "long/hard and fast" 12, 32, 56, 60, 63, 75 or "quick" 7, 21, 23, 58 breaths. The inhalation maneuver is one of the problematic steps that could potentially lead to errors with inhaled medication use, 84 and its effect on drug deposition has been reported in several studies. 8, 86 In studies using Diskus ® and Aerolizer ® , a "hard and deep" inhalation resulted in higher urinary salbutamol excretion and was recommended in patients with poor inspiratory effort, such as the elderly. 87, 88 In a separate study, patients using indacaterol Breezhaler ® (Neohaler ® ) were instructed to "inhale as hard and fast as they can from the start of the inhalation maneuver and for as long as possible" to maximize drug delivery. 32 PIF needs to be reached almost immediately (approximately 1 second) after the inhalation maneuver begins, and the achieved level of inspiration needs to be maintained during the entire inhalation maneuver (inspiratory profile) for effective drug release. A limitation of the In-Check™ Dial is that only PIF is measured, not the flow over the entire inspiratory profile or the timing in the inspiratory cycle when PIF is reached. Hence, at what time the patient is achieving PIF-in the first few seconds, when needed, or later-is not known. We recommend that patients should "inhale as fast, and as forcefully and deeply" as they can once their lips are sealed around the mouthpiece and should maintain this level of inhalation for as long as possible.

Finally, we recommend that a maximum of three consecutive measures should be used to determine the highest PIF versus the average of two or three measures; 89 appropriate hygiene instructions should be followed for the In-Check™ DIAL; 90 and the decision to assess PIF should be made by the healthcare provider based on patient-level information (eg, health status) and guidance set forth by organizations such as the American Thoracic Society regarding pulmonary function testing. 91, 92 We aimed to provide recommendations that are aligned with real-world experience and directions for performing spirometry [92] [93] [94] so that they are useful, practical, and ultimately beneficial to patients (Table 4 ; https://editage.share file.com/share/view/s744a7fee41d149bf9f345fd8d59291a7). Our recommendations are largely based on the In-Check™ DIAL; recommendations for other PIF measurement devices may differ. Suboptimal PIF (ie, PIF below the optimal threshold for the selected DPI) has been widely reported, 8, 12, 20, 23 can result in less than favorable outcomes, 9 and may be associated with hospital readmissions. 22 With an optimal PIF, sufficient dose of medication is more likely to be delivered, which should contribute to better clinical outcomes. Of note, however, the definition of "optimal" PIF for each individual DPI and the methods to measure PIF continue to be investigated.

Limitations to our evaluation include extrapolation from in vitro data and difficulty in providing a precise cutoff for the "suboptimal" PIF for each DPI. Findings from studies attempting to correlate suboptimal PIF with clinical outcomes were inconsistent. 22 

Our analysis of recommended and applied PIF assessment approaches revealed considerable variations in the way PIF is measured for the use of DPIs. Standardization of PIF measurements is needed because a patient's ability to generate an optimal IF is essential for effective drug delivery from a DPI. Based on current evidence, we recommend that while in a seated position, patients comfortably exhale slowly and fully, then inhale through the mouthpiece as fast and as forcefully and deeply as they can and maintain that level of inhalation for as long as possible. If adopted, these recommendations should yield PIF measurements that are conducted in a reproducible, standardized manner, which will help clinicians select the appropriate inhaler for each patient and, if selecting a DPI, help patients achieve the optimal PIF needed for effective drug dispersal and deposition.

COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; FDA, Food and Drug Administration; FRC, functional residual capacity; FVC, forced vital capacity; IF, inspiratory flow; PIF, peak inspiratory flow; pMDI, pressurized metered-dose inhaler; RV, residual volume; SMI, soft-mist inhaler. Pharmaceuticals, Inc. (BIPI) for these services. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

All authors contributed to the analysis and interpretation of data and critical review of the manuscript; agreed on the journal to which the manuscript will be submitted; reviewed and agreed on all versions of the manuscript before submission, during revision and the final version accepted for publication as well as any significant changes introduced at the proofing stage; and agree to take responsibility and be accountable for the contents of the article. Exhalation Breathe out slowly and fully Patients who exhale "fully and completely" could cause collapse of their small airways at low lung volumes. During the subsequent inhalation phase, the "energy" generated by the inhaled breath/volume has to overcome the "opening" of the collapsed small airways that have been induced by exhaling "fully and completely." The resultant energy available during inhalation to overcome airway collapse may be (not yet proven)

inadequate to generate the required inspiratory acceleration and energy necessary to optimally activate the DPI

Inhale as fast, forcefully, and deeply as you can once your lips are sealed around the mouthpiece and maintain this level of inhalation for as long as possible PIF needs to be reached almost immediately (approximately 1 second) after the inhalation maneuver begins, and the achieved level of inspiration needs to be maintained during the entire inhalation maneuver (inspiratory profile) for effective drug release 

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The authors meet the criteria for authorship as recommended by the International Committee of Medical Journal Editors. The authors received no direct compensation related to the development of the manuscript. Writing, editorial support, and formatting assistance was provided by Suchita Nath-Sain, PhD, and Maribeth Bogush, PhD, of Cactus Life Sciences (part of Cactus Communications), which was contracted and compensated by Boehringer Ingelheim

Writing, editorial support, and formatting assistance was contracted and compensated by Boehringer Ingelheim Pharmaceuticals, Inc. ( 

The International Journal of COPD is an international, peer-reviewed journal of therapeutics and pharmacology focusing on concise rapid reporting of clinical studies and reviews in COPD. Special focus is given to the pathophysiological processes underlying the disease, intervention programs, patient focused education, and self management protocols. This journal is indexed on PubMed Central, MedLine and CAS. The manuscript management system is completely online and includes a very quick and fair peer-review system, which is all easy to use. Visit http://www.dovepress.com/testimonials.php to read real quotes from published authors. Submit your manuscript here: https://www.dovepress.com/international-journal-of-chronic-obstructive-pulmonary-disease-journal

International Journal of Chronic Obstructive Pulmonary Disease 2022:17