Adherence to single inhaler triple therapy and digital inhalers in Chronic Obstructive Pulmonary Disease: a literature review and protocol for a randomized controlled trial (TRICOLON study).

BACKGROUND: Medication non-adherence is a significant problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Efforts to address this issue are receiving increased attention. Simplifying treatment by prescribing single-inhaler triple therapy (SITT) as an alternative to multi-inhaler triple therapy (MITT) or with smart inhalers are often considered potential solutions. However, the actual impact of these innovations on adherence and clinical outcomes is unclear. METHODS: To address this knowledge gap we first conducted a literature review focusing on two research questions: 1) the difference in adherence between SITT and MITT users in COPD, and 2) the effect of smart inhalers on adherence in COPD. Separate searches were conducted in PubMed and two authors independently assessed the articles. In addition, we present a protocol for a study to acquire knowledge for the gaps identified. RESULTS: To address the first research question, 8 trials were selected for further review. All trials were observational, i.e. randomized controlled trials were lacking. Seven of these trials showed higher adherence and/or persistence in patients on SITT compared with patients on MITT. In addition, four studies showed a positive effect of SITT on various clinical outcomes. For the second research question, 11 trials were selected for review. While most of the studies showed a positive effect of smart inhalers on adherence, there was considerable variation in the results regarding their effect on other clinical outcomes. The TRICOLON (TRIple therapy COnvenience by the use of one or multipLe Inhalers and digital support in ChrONic Obstructive Pulmonary Disease) trial aims to improve understanding regarding the effectiveness of SITT and smart inhalers in enhancing adherence. This open-label, randomized, multi-center study will enroll COPD patients requiring triple therapy at ten participating hospitals. In total, 300 patients will be randomized into three groups: 1) MITT; 2) SITT; 3) SITT with digital support through a smart inhaler and an e-health platform. The follow-up period will be one year, during which three methods of measuring adherence will be used: smart inhaler data, self-reported data using the Test of Adherence to Inhalers (TAI) questionnaire, and drug analysis in scalp hair samples. Finally, differences in clinical outcomes between the study groups will be compared. DISCUSSION: Our review suggests promising results concerning the effect of SITT, as opposed to MITT, and smart inhalers on adherence. However, the quality of evidence is limited due to the absence of randomized controlled trials and/or the short duration of follow-up in many studies. Moreover, its impact on clinical outcomes shows considerable variation. The TRICOLON trial aims to provide solid data on these frequently mentioned solutions to non-adherence in COPD. Collecting data in a well-designed randomized controlled trial is challenging, but the design of this trial addresses both the usefulness of SITT and smart inhalers while ensuring minimal interference in participants' daily lives. TRIAL REGISTRATION: NCT05495698 (Clinicaltrials.gov), registered at 08-08-2022. Protocol version: version 5, date 27-02-2023.

[Effects of Geriatric COPD rehabilitation on hospital admissions and exercise tolerance: a retrospective observational study]. / Effecten van geriatrische COPD-revalidatie op ziekenhuisopnames en inspanningstolerantie: een retrospectief observationele studie.

INTRODUCTION: Frail COPD patients are frequently not accepted for regular pulmonary rehabilitation programs due to low physical condition and functional limitations. Rehabilitation programs in nursing homes for geriatric patients with COPD have been developed. The effects of such programs are largely unknown. AIMS: To assess the course of COPD-related hospital admissions and exercise tolerance in a cohort of frail COPD patients participating in geriatric COPD rehabilitation. METHODS: Retrospective observational study with a follow up of 12 months after discharge from rehabilitation. COPD related hospital admission days were measured in the year before and after participating rehabilitation. Exercise tolerance was measured by the six minute walk test (6MWT) at admission and at discharge from rehabilitation. RESULTS: Fifty-eight participants accomplished the rehabilitation program. Twelve patients died in the first year after discharge. The median number of hospital admission days in the year before participating rehabilitation was 21 (IQR 10-33). The first year after discharge this was decreased to a median of 6 (IQR 0-12). The 6MWT increased from 194 (SD 85) meters at admission to 274 (SD 95) meters at discharge (mean difference 80 m, SD 72; p < 0.05). CONCLUSIONS: Geriatric COPD rehabilitation in a nursing home setting seems to reduce hospital admissions in frail COPD patients and to increase exercise tolerance.

Intubation after noninvasive ventilation failure in chronic obstructive pulmonary disease: associated factors at emergency department presentation.

OBJECTIVE: Noninvasive ventilation (NIV) is a common practice in acute hypercapnic respiratory failure (AHRF) because of exacerbation of chronic obstructive pulmonary disease (COPD). However, a recent study has shown that patients who require invasive mechanical ventilation (IMV) after failure of NIV experience high mortality rates (up to 30%). Therefore, the aim of this study is to determine the parameters, specifically for emergency department (ED) presentation, associated with the transition from NIV to IMV because of NIV failure. PATIENTS AND METHODS: This is a 4-year retrospective cohort study in the EDs of two Dutch hospitals. International Classification of Disease codes were used to identify 139 COPD patients treated with NIV. Those with AHRF (pH limits: 7.25-7.35), a full resuscitation order, and those without a pneumonia were selected for the study (n=40 with 50 NIV episodes). Parameters in patients treated successfully with NIV were compared with those in patients requiring transition to IMV due to NIV failure. Univariable regression analysis was used and, if P-value less than 0.20, analyses were entered into a multivariable logistic regression analysis model. RESULTS: NIV was successful in 33 (66%) patients, 10 (20%) required transition to IMV, and seven (14%) died. Age over 65 years and a Glasgow Coma Score less than 15 were associated significantly with the transition from NIV to IMV in multivariable analysis (P<0.05). CONCLUSION: Older age and a low Glasgow Coma Score at ED presentation are factors associated with the transition from NIV to IMV in COPD patients with AHRF.

Discontinuation of furosemide decreases PaCO(2) in patients with COPD.

STUDY OBJECTIVE: To evaluate whether the discontinuation of furosemide treatment resulted in a decrease in PaCO(2) and an increase in daytime and nocturnal oxygenation. BACKGROUND: Furosemide is widely prescribed in patients with COPD for the treatment of peripheral edema. It is known that furosemide causes a metabolic alkalosis. A diminished chemoreceptor stimulation may cause a decreased alveolar ventilation. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial. SETTING: Department of Pulmonology, Rijnstate Hospital Arnhem, the Netherlands. PATIENTS: Twenty patients with stable COPD (10 men; median age, 70 years [range, 58 to 81 years]; FEV(1) 35% predicted [range, 19 to 70% predicted]). Subjects were included if they had received furosemide, 40 mg/d, for the treatment of peripheral edema for at least a month and if they had a mean nocturnal arterial oxygen saturation (SaO(2)) < 92%. Patients with cardiac left and/or right ventricular dysfunction, sleep apneas, and patients receiving other diuretics, angiotensin-converting enzyme inhibitors, potassium or chloride replacement therapy, or long-term oxygen treatment were excluded. INTERVENTION: Furosemide was discontinued for 1 week and replaced by placebo treatment in the first or the second week. MEASUREMENTS AND RESULTS: Ventilation, daytime arterial blood gas levels, and nocturnal SaO(2) were measured at baseline, after 1, and after 2 weeks. Sixteen subjects completed the study. Ventilation increased from 10.4 L/min (range, 6.7 to 15.4 L/min) at baseline to 11.6 L/min (range, 8.7 to 14.0 L/min) after discontinuation of furosemide (p < 0.05). PaCO(2) decreased from 45 mm Hg (range, 35 to 64 mm Hg) to 41 mm Hg (range, 32 to 61 mm Hg; p < 0.01). Daytime and nocturnal oxygenation did not improve. CONCLUSIONS: Although it does not improve oxygenation, the discontinuation of furosemide decreases PaCO(2) in patients with COPD.