The Intention of Inhaled Medication Adherence Scale (IMAS): The Development of a New Instrument for Assessing Inhaled Medication Adherence Among Patients with Chronic Obstructive Pulmonary Disease (COPD) Using Theory of Planned Behavior.

Purpose: Inhaled medication adherence is an important issue for patients with chronic obstructive pulmonary disease (COPD) because adhering to inhaled medications could substantially improve their health. However, patients with COPD may not be always adhere to the prescribed inhaled medications. Therefore, understanding the underlying reasons for patients with COPD adhering to inhaled medications is important. The present study used Theory of Planned Behavior (TPB) as a theoretical framework to develop the Intention of Inhaled Medication Adherence Scale (IMAS) and assess its psychometric properties. Patients and Methods: After reviewing papers using the TPB to design psychometric scales and the TPB scale development guidelines, 28 items were generated for expert evaluation. Eight experts reported that the 28 items all had good content validity (content validity index ranged from 0.88 to 1.00 at item-level; and from 0.981 to 0.987 at scale-level) comprising four factors. Following initial development, 235 patients with COPD (mean age 73.12 years; 93.6% males) completed the IMAS via interview with a respiratory therapist and a research assistant. The four-factor structure of the IMAS was evaluated using confirmatory factor analysis (CFA). Results: Nine IMAS items were removed because of low factor loadings or offending estimates. The 19-item IMAS was confirmed as having a four-factor structure supported by the CFA results (comparative fit index=1.00; Tucker-Lewis index=1.00; root mean square error of approximation=0.00; standardized root mean square residual=0.06). Conclusion: The 19-item IMAS had satisfactory psychometric properties in construct validity. The 19-item IMAS is an instrument that could help healthcare providers understand potential factors associated with adherence to inhaled medications among people with COPD.

Influence of Aerosol Mask Design on Fugitive Aerosol Concentrations During Nebulization.

BACKGROUND: Secondhand exposure to fugitive aerosols may cause airway diseases in health providers. We hypothesized that redesigning aerosol masks to be closed-featured would reduce the fugitive aerosol concentrations during nebulization. This study aimed to evaluate the influence of a mask designed for a jet nebulizer on the concentration of fugitive aerosols and delivered doses. METHODS: An adult intubation manikin was attached to a lung simulator to mimic normal and distressed adult breathing patterns. The jet nebulizer delivered salbutamol as an aerosol tracer. The nebulizer was attached to 3 aerosol face masks: an aerosol mask, a modified non-rebreathing mask (NRM, with no vent holes), and an AerosoLess mask. An aerosol particle sizer measured aerosol concentrations at parallel distances of 0.8 m and 2.2 m and a frontal distance of 1.8 m from the manikin. The drug dose delivered distal to the manikin's airway was collected, eluted, and analyzed using a spectrophotometer at a 276 nm wavelength. RESULTS: With a normal breathing pattern, the trends of aerosol concentrations were higher with an NRM followed by an aerosol mask and AerosoLess mask (P < .001) at 0.8 m; however, the concentrations were higher with an aerosol mask followed by NRM and AerosoLess mask at 1.8 m (P < .001) and 2.2 m (P < .001). With a distressed breathing pattern, the aerosol concentrations were higher with an aerosol mask followed by an NRM and AerosoLess mask at 0.8 m, 1.8 m (P < .001), and 2.2 m (P = .005). The delivered drug dose was significantly higher with AerosoLess mask with a normal breathing pattern and with an aerosol mask with a distressed breathing pattern. CONCLUSIONS: Mask design influences fugitive aerosol concentrations in the environment, and a filtered mask reduces the concentration of aerosols at 3 different distances and with 2 breathing patterns.

Predicting Inhaled Drug Dose Generated by Mesh Nebulizers.

Background: The lung dose of nebulized drugs for spontaneous breathing is influenced by breathing patterns and nebulizer performance. This study aimed to develop a system for measuring breath patterns and a formula for estimating inhaled drugs, and then to validate the hypothesized prediction formula. Methods: An in vitro model was first used to determine correlations among the delivered dose, breath patterns, and doses deposited on the accessories and reservoirs testing with a breathing simulator to generate 12 adult breathing patterns (n = 5). A pressure sensor was developed to measure breathing parameters and used along with a prediction formula that accounted for the initial charge dose, respiratory pattern, and dose on the accessory and reservoir of a nebulizer. Three brands of nebulizers were tested by placing salbutamol (5.0 mg/2.5 mL) in the drug holding chamber. Ten healthy individuals participated in the ex vivo study to validate the prediction formula. The agreement between the predicted and inhaled doses was analyzed using the Bland-Altman plot. Results: The in vitro model showed that the inspiratory time to total respiratory cycle time (Ti/Ttotal; %) was significantly directly correlated with the delivered dose among the respiratory factors, followed by inspiratory flow, respiratory rate, and tidal volume. The ex vivo model showed that Ti/Ttotal was significantly directly correlated with the delivered dose among the respiratory factors, in addition to the nebulization time and accessory dose. The Bland-Altman plots for the ex vivo model showed similar results between the two methods. Large differences in inhaled dose measured at the mouth were observed among the subjects, ranging from 12.68% to 21.68%; however, the difference between the predicted dose and inhaled dose was lower, at 3.98%-5.02%. Conclusions: The inhaled drug dose could be predicted with the hypothesized estimation formula, which was validated by the agreement between the inhaled and predicted doses of breathing patterns of healthy individuals.

Identifying Novel Clusters of Patients With Prolonged Mechanical Ventilation Using Trajectories of Rapid Shallow Breathing Index.

Objective: Patients with prolonged mechanical ventilation (PMV) are comprised of a heterogeneous population, creating great challenges for clinical management and study design. The study aimed to identify subclusters of PMV patients based on trajectories of rapid shallow breathing index (RSBI), and to develop a machine learning model to predict the cluster membership based on baseline variables. Methods: This was a retrospective cohort study conducted in respiratory care center (RCC) at a tertiary academic medical center. The RCC referral criteria were patients with mechanical ventilation for at least 21 days with stable hemodynamic and oxygenation status. Patients admitted to the RCC from April 2009 to December 2020 were screened. Two-step clustering through linear regression modeling and k-means was employed to find clusters of the trajectories of RSBI. The number of clusters was chosen by statistical metrics and domain expertise. A gradient boosting machine (GBM) was trained, exploiting variables on RCC admission, to predict cluster membership. Results: A total of 1371 subjects were included in the study. Four clusters were identified: cluster A showed persistently high RSBI; cluster B was characterized by a constant low RSBI over time; Cluster C was characterized by increasing RSBI; and cluster D showed a declining RSBI. Cluster A showed the highest mortality rate (72%), followed by cluster D (63%), C (62%) and B (61%; p = 0.005 for comparison between 4 clusters). GBM was able to predict cluster membership with an accuracy of > 0.95 in ten-fold cross validation. Highly ranked variables for the prediction of clusters included thyroid-stimulating hormone (TSH), cortisol, platelet, free thyroxine (T4) and serum magnesium. Conclusions: Patients with PMV are composed of a heterogeneous population that can be classified into four clusters by using trajectories of RSBI. These clusters can be easily predicted with baseline clinical variables.

Effects of pulmonary rehabilitation program on amyotrophic lateral sclerosis: A meta-analysis of randomized controlled trials.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) develop respiratory failure and progressive muscle weakness. The effects of pulmonary rehabilitation on the lung function of patients with ALS are unclear. OBJECTIVE: Through this meta-analysis of randomized controlled trials (RCTs), we evaluated the effects of pulmonary rehabilitation, such as type of treatment, on patients with ALS and compared the effectiveness of this treatment. METHODS: PubMed, EMBASE, Web of Science, and Cochrane databases were searched until December 2020. The methodological quality of each study was assessed using the updated Cochrane Risk of Bias tool (RoB 2.0). Data were analyzed using Review Manager version 5.4 (Cochrane Collaboration, Oxford, England), and the meta-analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: Of 2168 articles, 10 trials were reviewed; among these trials, two focused on respiratory training and eight on physical exercise, three of which involved a combination of aerobic and resistance training. Our meta-analysis demonstrated no difference in the ALSFRS-R score and % FVC among patients with ALS. CONCLUSIONS: Respiratory training or physical exercise did not significantly affect the ALSFRS-R score and % FVC of patients with ALS. At 12 months after intervention, the ALSFRS-R score in the physical exercise group was higher than that in the usual care group. Further clinical trials are warranted to develop approaches for improving the lung function of patients with ALS.

Evidence-searching capability among health care professionals: a comparative study.

BACKGROUND: Evidence-based practice is among core competencies of health care professionals (HCPs). However, the levels of evidence-searching capability may differ among various disciplines of HCPs as they receive different education and trainings for various durations in medical schools and teaching hospitals. METHODS: This study aimed to compare the evidence-searching capability among different disciplines of HCPs and identify which aspects need to be reinforced. From a teaching hospital, we recruited 80 HCPs of various disciplines and compared their evidence-searching capability by using a validated scale. To examine if sex and education levels affect evidence-searching capability, we performed a multiple linear regression analysis with collinearity diagnostics. RESULTS: Physicians and pharmacists performed significantly better than other disciplines in the seven formative assessment items and the summative item (all P < 0.05). No collinearity was detected between discipline and age nor level of education. Except for the 2nd formative assessment item (correlation coefficient 0.24 ± 0.12, P = 0.04), participant's levels of education did not affect evidence-searching capability. Age was associated with lower evidence-searching capability in five formative and the summative assessment items. CONCLUSIONS: We found a better evidence-searching capability among physicians and pharmacists than other HCPs who may require more training on evidence-searching skills. Also, evidence-searching skills training should be provided to HCPs irrespective of age and education levels.

Benefits of Multiple-Intervention Pulmonary Rehabilitation to Older Adults with High-Risk Multimorbidity after Coronary Artery Bypass Grafting.

OBJECTIVE: Multimorbidity in elderly patients increases complications and retards the recovery of pulmonary function after coronary artery bypass grafting (CABG) surgery. We aimed to evaluate the impact of multiple-intervention pulmonary rehabilitation (PR) on respiratory muscle strength and dyspnea scores after CABG in adult patients aged ≥65 years who had multimorbidity. METHODS: A cohort study was retrospectively conducted with 95 adults aged ≥65 years who underwent CABG surgery and completed a multiple-intervention PR program. RESULTS: Patients in the non-multimorbidity (n = 56) and multimorbidity groups (n = 39) were evaluated on the basis of their muscle strength, degree of dyspnea, and pulmonary function. Postoperative complications were compared after the completion of PR. Between extubation days 1 and 14, the multimorbidity group showed significant improvements in maximal inspiratory pressure (16.91 vs. 24.95 cmH2O, P < 0.001), Borg Scale score (0.99 vs. 2.3, P < 0.001), and the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC ratio) of 7.02% vs. 13.4% (P = 0.01). The incidence rates of pulmonary complications were similar between the two groups. CONCLUSIONS: Multi-interventional PR program significantly improved the maximal inspiratory pressure, Borg scale score, and FEV1/FVC ratio in the adult patients aged ≥65 years who had multimorbidity after undergoing CABG surgery.

Effect of high flow nasal cannula on peripheral muscle oxygenation and hemodynamic during paddling exercise in patients with chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND: Exercise training for patients with chronic obstructive pulmonary disease (COPD) improves their endurance and oxygenation. Supplemental oxygen delivered by high flow nasal cannula (HFNC) reportedly improves the clinical outcomes during high-intensity exercise. However, the physical benefits of the provision of supplemental oxygen with HFNC for the improvement of exercise performance have not been fully investigated. This randomized trial aimed to evaluate the effect of HFNC on the hemodynamic status and peripheral muscle microcirculation during exercise training. METHODS: In this multicenter, randomized controlled parallel two-group study, 32 patients with moderate to severe COPD were randomly assigned into the nasal cannula (NC) group (n=15) with a flow rate of 2-3 L/min or the HFNC group (n=17) with a flow rate of 45 L/min for twelve 40 min exercise training sessions. RESULTS: The mean cardiac index (CI) and stroke volume (SV) of the NC group in the first session were significantly lower than those of the HFNC group (3.68±0.76 vs. 4.5±0.76 L/min/m2, P=0.014; 63.03±9.87 vs. 74.22±19.48, P=0.002, respectively). The systemic vascular resistance (SVR) of the NC group was significantly lower in the seventh session than in the first session (891±287 vs. 1,138±381 dyn-s/cm5, respectively, P=0.048). The mean deoxyhemoglobin level was higher in the HFNC group in the 1st session and lower in the 12th session (1.09±9.04 vs. 7.3±7.3 µm, P=0.046). The COPD Assessment Test score, Modified Medical Research Council scale score, maximum inspiratory pressure (MIP), and maximum expiratory pressure were different within and between the groups. CONCLUSIONS: HFNC, with a lower oxygen concentration than that used with a traditional NC, yielded lower deoxygenated hemoglobin levels after 12 suboptimal exercise training sessions. In contrast, the higher oxygen concentration delivered by NC reduced SVR. The COPD assessment score improved on exercise training, regardless of the supplemental oxygen delivery method.

Optimal Connection for Tiotropium SMI Delivery through Mechanical Ventilation: An In Vitro Study.

We aimed to quantify Soft Mist Inhalers (SMI) delivery to spontaneous breathing model and compare with different adapters via endotracheal tube during mechanical ventilation or by manual resuscitation. A tiotropium SMI was used with a commercial in-line adapter and a T-adapter placed between the Y-adapter and the inspiratory limb of the ventilator circuit during mechanical ventilation. The SMI was actuated at the beginning of inspiration and expiration. In separate experiments, a manual resuscitator with T-adapter was attached to endotracheal tube, collecting filter, and a passive test lung. Drug was eluted from collecting filters with salt-based solvent and analyzed using high-performance liquid chromatography. Results showed the percent of SMI label dose inhaled was 3-fold higher with the commercial in-line adapter with actuation during expiration than when synchronized with inspiration. SMI with T-adapter delivery via ventilator was similar to inhalation (1.20%) or exhalation (1.02%), and both had lower delivery dose than with manual resuscitator (2.80%; p = 0.01). The inhaled dose via endotracheal tube was much lower than inhaled dose with spontaneous breathing (22.08%). In conclusion, the inhaled dose with the commercial adapter was higher with SMI actuated during expiration, but still far less than reported spontaneous inhaled dose.

A scale for measuring evidence-searching capability: A development and validation study.

RATIONALE: The ability to acquire the best evidence efficiently is an important competency for busy health-care professionals who must make decisions quickly. AIMS AND OBJECTIVES: We aimed to develop and validate a scale for measuring evidence-searching capability. METHODS: We first developed a scale for measuring evidence-searching capability by using the modified Delphi technique. Seven experts commented on a draft 33-item scale on a 5-point scale. All items rated less than three by any expert were removed. The items were modified or merged considering experts' feedback. When all items were rated greater than or equal to 3 by all experts with an interquartile range of less than or equal to 1, a consensus on the scale was achieved with the content validity constructed. We performed a pilot test and a formal test, and evaluated the inter-rater, intra-rater, and internal reliability by calculating the intra-cluster correlation coefficient (ICC), kappa correlation coefficient, and Cronbach's α. RESULTS: We developed a scale consisted of 15 items and a global rating score, with an average scale-content validity index of 0.98. In the pilot test, the ICC for inter-rater and intra-rater reliability was 0.91 and 1, respectively. The Cronbach's α was 0.90. In the formal test, the ICC for inter-rater reliability ranged from 0.61 to 1 and the weighted kappa correlation coefficient ranged from 0.27 to 1, with a Cronbach's α of 0.97. CONCLUSIONS: This study is the first to develop and validate a scale for measuring evidence-searching skills through a systematic approach. The scale is composed of 15 items and a global rating score that can be easily used in objective assessment of knowledge-acquiring ability.

Aerosol delivery during spontaneous breathing with different types of nebulizers- in vitro/ex vivo models evaluation.

BACKGROUND: Nebulizers for spontaneous breathing have been evaluated through different study designs. There are limitations in simulated bench models related to patient and nebulizer factors. The aim of this study was to determine the correlation of inhaled drug mass between in vitro and ex vivo studies by testing aerosol deposition of various types of nebulizers. METHODS: Ten healthy subjects were recruited to receive aerosol therapy with five nebulizers in random order: 1) a jet nebulizer (JN); 2) a breath-enhanced nebulizer (BEN); 3) a manually triggered nebulizer (MTN), 4) a breath-actuated nebulizer (BAN), and 5) a vibrating mesh nebulizer (VMN) with valved-adapter. A unit dose of salbutamol containing 5 mg in 2.5 mL was placed into the nebulizer and administered for 10 min. For the ex vivo study, minute ventilation of healthy subjects was recorded for 1 min. For the in vitro study a breathing simulator was utilized with adult breathing patterns. Aerosolized drug from the nebulizers and the accessory tubes was captured using inspiratory and expiratory collecting filters. Captured drug was eluted, measured and expressed as inhaled and exhaled mass using spectrophotometry at a wavelength of 276 nm. RESULTS: 10 healthy subjects were recruited, aged 20.8 ±â€¯0.7 years old, with a mean height of 166.2 ±â€¯9.2 cm and weight of 64.7 ±â€¯12.4 kg. There was no significant difference in the inhaled drug dose between the JN and BEN (15.0 ±â€¯1.94% and 17.74 ±â€¯2.65%, respectively, p = .763), yet the inhaled doses were lower than the other three nebulizers (p < .001). The VMN delivered greater inhaled dose than the other four nebulizers (p < .01). The respiratory rate of the cohorts was significantly correlated with the inhaled drug dose. For the in vitro model, the JN delivered a lower inhaled dose (11.6 ±â€¯1.6, p < .001) than the other nebulizers, whereas the MTN and BAN deposited significantly lower exhaled doses (1.7 ±â€¯0.4 and 2.7 ±â€¯0.2, respectively, p < .001). The VMN demonstrated a greater drug dose with the in vitro study than the ex vivo model (44.0 ±â€¯0.9% and 35.5 ±â€¯6.3% respectively, p = .003), whereas the JN in the ex vivo model resulted in a greater inhaled drug dose (15.0 ±â€¯1.9% for ex vivo vs 11.6 ±â€¯1.6% for in vitro, p = .008). CONCLUSIONS: These in vitro/ex vivo model comparisons of nebulizers performance indicated that breath-related nebulizers can be estimated using an in vitro model; however, the JN and VMN delivered inhaled drug mass differed between models. There was a significant correlation between respiratory rate and inhaled mass, and the inhaled drug dose generated by VMN correlated with minute ventilation. This study demonstrated that the VMN produced greater inhaled drug dose and lowest residual dose, whereas the BEN, BAN, and MTN produced lower exhaled drug dose in both in vitro and ex vivo models.

Size distribution of salbutamol/ipratropium aerosols produced by different nebulizers in the absence and presence of heat and humidification.

BACKGROUND: Few studies have evaluated the size distribution of inhaled and exhaled aerosolized drugs, or the effect of heated humidification on particle size and lung deposition. The present study evaluated these aspects of bronchodilator (salbutamol/ipratropium) delivery using a lung model in the absence and presence of heat and humidification. METHODS: We positioned filters to collect and measure the initial drug, inhaled drug, and exhaled drug. Particle size distribution was evaluated using an 8-stage Marple personal cascade impactor with 0.2-µm polycarbonate filters. RESULTS: A greater inhaled drug mass was delivered using a vibrating mesh nebulizer (VMN) than by using a small volume nebulizer (SVN), when heated humidifiers were not employed. When heated and humidified medical gas was used, there was no significant difference between the inhaled drug mass delivered by the VMN and that delivered by the SVN. A significantly greater mass of inhaled 1.55-µm drug particles was produced by the VMN than with the SVN, under heated and humidified conditions. However, the mass median aerodynamic diameters (MMADs) of the aerosolized drug produced by the SVN and VMN did not differ significantly under the same conditions. CONCLUSIONS: The VMN produced more fine particles of salbutamol/ipratropium, and the drug particle size clearly increased in the presence of heat and humidification.

Burden on caregivers of ventilator-dependent patients: A cross-sectional study.

Caring for prolonged mechanical ventilation (PMV) patients imposes heavy psychological, physical, social, and financial burdens on caregivers. Currently, studies regarding the burden on caregivers of PMV patients are scant; therefore, the present study investigated the burden on caregivers of PMV patients.This cross-sectional study was approved by the Institutional Review Board of Zuoying Armed Forces General Hospital. A survey was conducted among the caregivers of PMV patients who were admitted to a chronic respiratory care ward (RCW) or were receiving home care from June to December 2010. The survey included basic demographic information of PMV patients and their caregivers and the Burden Assessment Scale scores for 4 domains comprising a total of 21 questions (physical burden, n = 5; psychological burden, n = 6; social burden, n = 6; financial burden, n = 4). Statistical analyses were conducted using the t test, 1-way analysis of variance with the Scheffé post hoc test, and the chi-square test, and P < .05 was considered statistically significant.A total of 160 caregivers (age, 50-53 years) were recruited (n = 80 each in the home care and RCW groups), and most of these caregivers were married women. Due to insufficient sleep, physical exhaustion, back pain, and caregiving, home caregivers had significantly higher physical burden levels than RCW caregivers (P < .01).Home caregivers experienced higher physical burden levels than RCW caregivers. Therefore, clinical and professional support must be provided to home caregivers of PMV patients.

Aerosol Delivery Using Jet Nebulizer and Vibrating Mesh Nebulizer During High Frequency Oscillatory Ventilation: An In Vitro Comparison.

BACKGROUND: High frequency oscillatory ventilation (HFOV) is used in critically ill patients with severe hypoxemic respiratory failure. The purpose of this in vitro study was to determine the efficiency of aerosol delivery with different lung parameters during simulated neonatal, pediatric, and adult HFOV. METHODS: Sensormedics 3100A/B ventilators were used to deliver infant, pediatric, and adult HFOV. Two types of aerosol generators were chosen for testing: 1) a continuous jet nebulizer (JN) with a unit-dose of 5.0 mg/2.5 mL salbutamol sulfate diluted into 4 mL, and 2) a vibrating mesh nebulizer (VMN) with salbutamol sulfate were run to completion of aerosol generation. Both aerosol devices were placed 1) between the ventilator circuit and the endotracheal tube (ETT) (proximal position); and 2) at the inlet of the heated humidifier (distal position) (n = 5). Drug was collected on a bacterial filter placed distal to the ETT, and the drug eluted and analyzed with a UV Spectrophotometer at 276 nm. T- test and ANOVA tests were used for comparison (p < 0.05). RESULTS: The inhaled drug delivered by JN was 0%-0.6% of the nominal dose when placed at distal position, and 0%-3% at proximal position (p < 0.01), while the VMN was 0%-0.5% at distal and 8.6%-22.7% at proximal position (p < 0.01). Aerosol delivery during HFOV was greater with adult settings than pediatric and infant settings with VMN and JN (22.7%, 8.6%, and 17.4% respectively, p < 0.01). When the aerosol delivery device was placed at the distal position, negligible drug mass was observed (<0.5%), regardless of the nebulizer device used. CONCLUSIONS: During HFOV, aerosol delivery with the nebulizer placed at proximal was greater than placement distal from the ETT, with VMN delivering more drug than JN. The inhaled drug was delivery correlated positively with ETT size, MAP, and bias flow, and inversely proportional to power settings.