A Research Agenda to Improve Outcomes in Patients with Chronic Obstructive Pulmonary Disease and Cardiovascular Disease. An Official American Thoracic Society Research Statement.

BACKGROUND: Individuals with chronic obstructive pulmonary disease (COPD) are often at risk for or have comorbid cardiovascular disease and are likely to die of cardiovascular-related causes. OBJECTIVES: To prioritize a list of research topics related to diagnosis and management of patients with COPD and comorbid cardiovascular diseases (heart failure, atherosclerotic vascular disease and atrial fibrillation) by summarizing existing evidence and using consensus-based methods. METHODS: A literature search was performed. References were reviewed by committee co-chairs. An international, multidisciplinary committee, including a patient advocate, met virtually to review evidence and identify research topics. A modified Delphi approach was used to prioritize topics in real-time based on their potential for advancing the field. RESULTS: Gaps spanned the translational science spectrum from basic science to implementation: 1) disease mechanisms, 2) epidemiology, 3) subphenotyping, 4) diagnosis and management, 5) clinical trials, 6) care delivery, 7) medication access, adherence and side effects, 8) risk factor mitigation, 9) cardiac and pulmonary rehabilitation, and 10) health equity. Seventeen experts participated and quorum was achieved for all votes (>80%). Of 17 topics, ≥70% agreement was achieved for 12 topics after 2 rounds of voting. Range of summative Likert score was -15 to 25. Highest priority was "Conduct pragmatic clinical trials with patient-centered outcomes that collect both pulmonary and cardiac data elements." Health equity was identified as an important topic that should be embedded within all research. CONCLUSIONS: We propose a prioritized research agenda with the purpose of stimulating high-impact research that will hopefully improve outcomes among people with COPD and cardiovascular disease.

Association between a Recalled Positive Airway Pressure (PAP) Device and Incident Cancer: A Population-Based Study.

BACKGROUND: The real-world consequences of a Philips/Respironics recall for positive airway pressure (PAP) devices distributed between 2009 and 2021 are unknown. METHODS: We conducted a retrospective population-based study using health administrative databases (Ontario, Canada) on all new adult PAP users identified through the provincial funding system, free of cancer at baseline, who initiated (claimed) PAP treatment between 2012 and 2018. Everyone was followed from the PAP claim date to the earliest of incident cancer diagnosis, death, or the end of the follow-up (March 2022). We used inverse probability of treatment weighting to balance baseline characteristics between individuals on recalled devices and those on devices from other manufacturers. Weighted hazard ratios of incident cancer were compared between groups. RESULTS: Of 231 692 individuals identified, 58 204 (25.1%) claimed recalled devices, and 173 488 (74.9%) from other manufacturers. A meaningful baseline difference between groups (standardised difference≥0.10) was noted only by location-relevant covariates; other variables were mostly equally distributed (standardised differences≤0.06). Over a median follow-up of 6.3 years (IQR: 4.9-8.0), 11 166 (4.8%) developed cancer: unadjusted rates per 10 000 Person-Year (95 CI%) of 78.8 (76.0-81.7) in the recall group versus74.0 (72.4-75.6) in others (p=0.0034). Propensity score weighting achieved excellent balance in baseline characteristics between groups (standardised differences≤0.07). On a weighted sample, there was no statistical difference in the hazard of incident cancer between groups: cause-specific hazard ratio (recalled versus others) of 0.97, 95% CI: 0.89-1.06. CONCLUSION: In our real-world population study, compared to other manufacturers and adjusting for confounders, recalled devices do not appear to be independently associated with developing cancer.

Early versus late onset interstitial lung disease in rheumatoid arthritis: An observational study of risk factors and mortality in Ontario, Canada.

BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) can occur as a manifestation of rheumatoid arthritis (RA) at various times in the disease course. We aimed to identify factors associated with early versus late onset RA-ILD and how the timing of RA-ILD influenced surgical lung biopsy completion and mortality. METHODS: We performed a retrospective observational study using health services data from Ontario, Canada. We identified RA cases between 2000 and 2020 using the Ontario Rheumatoid Arthritis Database. RA-ILD diagnosis required repeat physician visits for ILD, with early RA-ILD defined as within 1 year of RA diagnosis. We performed multivariable logistic regression to identify factors associated with early RA-ILD and surgical lung biopsy completion, and multivariable cox-proportional hazards regression to evaluate the association of early versus late RA-ILD on all-cause and RA-ILD related mortality. RESULTS: In total, we identified 3717 cases of RA-ILD. Older age at RA diagnosis [OR 1.04 (95%CI 1.03-1.05), p < 0.0001], female sex [OR 1.16 (95%CI 1.01-1.35), p = 0.04] and immigrating to Ontario [OR 1.70 (95%CI 1.35-2.14), p < 0.0001] was associated with early RA-ILD. Patients with early versus late RA-ILD experienced similar odds of undergoing a surgical lung biopsy [OR 1.34 (95%CI 0.83-2.16), p = 0.23]. Early RA-ILD was associated with increased all-cause mortality [HR 1.17 (95%CI 1.07-1.29), p = 0.0009], primarily driven by an increase in RA-ILD related mortality [HR 1.45 (95%CI 1.19-1.76), p = 0.0003]. CONCLUSION: Age at RA onset, female sex and immigration status are associated with early RA-ILD. Patients with early RA-ILD experience increased all-cause and RA-ILD related mortality after adjusting for demographics and comorbidities.

Impact of surgical lung biopsy on lung function and survival in patients with idiopathic pulmonary fibrosis in a multi-centre registry cohort.

BACKGROUND AND OBJECTIVE: Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non-negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis. METHODS: Linear mixed models and Cox proportional hazards regression models were used to compare decline in forced vital capacity (FVC)%, diffusion capacity of the lung (DLCO%) and risk of death or lung transplantation between SLB and non-SLB patients. Adjustments were made for baseline age, sex, smoking history, antifibrotic use, and lung function. A similar analysis compared lung function changes 12 months pre- and post-SLB. RESULTS: A total of 81 SLB patients and 468 non-SLB patients were included. In the SLB group, the post-biopsy annual FVC% decline was 2.0% (±0.8) in unadjusted, and 2.1% (±0.8) in adjusted models. There was no difference in FVC% decline, DLCO% decline, or time to death or lung transplantation between the two groups, in adjusted or unadjusted models (all p-values >0.07). In the pre-post SLB group, no differences were identified in FVC% decline in unadjusted or adjusted models (p = 0.07 for both). CONCLUSION: No association between SLB and lung function decline or risk of death or lung transplantation was identified in this multi-centre study of patients with IPF.

Feasibility of a wearable self-management application for patients with COPD at home: a pilot study.

BACKGROUND: Among people with COPD, smartphone and wearable technology may provide an effective method to improve care at home by supporting, encouraging, and sustaining self-management. The current study was conducted to determine if patients with COPD will use a dedicated smartphone and smartwatch app to help manage their COPD and to determine the effects on their self-management. METHODS: We developed a COPD self-management application for smartphones and smartwatches. Participants were provided with the app on a smartphone and a smartwatch, as well as a cellular data plan and followed for 6 months. We measured usage of the different smartphone app functions. For the primary outcome, we examined the change in self-management from baseline to the end of follow up. Secondary outcomes include changes in self-efficacy, quality of life, and COPD disease control. RESULTS: Thirty-four patients were enrolled and followed. Mean age was 69.8 years, and half of the participants were women. The most used functions were recording steps through the smartwatch, entering a daily symptom questionnaire, checking oxygen saturation, and performing breathing exercises. There was no significant difference in the primary outcome of change in self-management after use of the app or in overall total scores of health-related quality of life, disease control or self-efficacy. CONCLUSION: We found older patients with COPD would engage with a COPD smartphone and smartwatch application, but this did not result in improved self-management. More research is needed to determine if a smartphone and smartwatch application can improve self-management in people with COPD. TRIAL REGISTRATION: ClinicalTrials.Gov NCT03857061, First Posted February 27, 2019.

Impressions and Perceptions of a Smartphone and Smartwatch Self-Management Tool for Patients With COPD: A Qualitative Study.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often do not seek care until they experience an exacerbation. Improving self-management for these patients may increase health-related quality of life and reduce hospitalizations. Patients are willing to use wearable technology for real-time data reporting and perceive mobile technology as potentially helpful in COPD management, but there are many barriers to the uptake of these technologies. OBJECTIVE: We aimed to understand patients' experiences using a wearable and mobile app and identify areas for improvement. METHODS: We conducted semi-structured interviews as part of a larger prospective cohort study wherein patients used a wearable and app for 6 months. We asked which features patients found accessible, acceptable and useful. RESULTS: We completed 26 interviews. We summarized our research findings into four main themes: (1) information, support and reassurance, (2) barriers to adoption, (3) impact on communication with health care providers, and (4) opportunities for improvement. Most patients found the feedback received through the app to be reassuring and useful. Some patients experienced technical difficulties with the app and found the wearable to be uncomfortable. CONCLUSIONS: Patients found a wearable device and mobile application to be acceptable and useful for the management of COPD. We identified barriers to adoption and opportunities for improvement to the design of our app. Further research is needed to understand what people with COPD and their healthcare providers want and will use in a mobile app and wearable for COPD management.

Association of clinically significant obstructive sleep apnoea with risks of contracting COVID-19 and serious COVID-19 complications: a retrospective population-based study of health administrative data.

RATIONALE/OBJECTIVES: Despite plausible pathophysiological mechanisms, more research is needed to confirm the relationship between obstructive sleep apnoea (OSA) and the risk of COVID-19 infection or COVID-19-related serious complications. METHODS: We conducted a retrospective population-based cohort study using provincial health administrative data (Ontario, Canada). Adults with physician-diagnosed OSA who received positive airway pressure therapy in the 5 years prepandemic (OSA group) were propensity score matched by baseline characteristics to individuals in the general population at low risk of OSA (non-OSA group) using inverse probability of treatment weighting. Weighted HRs of (1) a positive COVID-19 test and (2) COVID-19-related emergency department (ED) visits, hospitalisations, intensive care unit (ICU) admissions and mortality, within 12 months of pandemic onset, were compared between groups. We also evaluated the impact of comorbid cardiometabolic or chronic airways disease. RESULTS: We identified and matched 324 029 individuals in the OSA group to 4 588 200 individuals in the non-OSA group. Compared with the non-OSA group, those in the OSA group were at a greater hazard of testing positive for COVID-19 (HR=1.17, 95% CI 1.13 to 1.21), having a COVID-19-related ED visit (HR=1.62, 95% CI 1.51 to 1.73), hospitalisation (HR=1.50, 95% CI 1.37 to 1.65) or ICU admission (HR=1.53, 95% CI 1.27 to 1.84). COVID-19-related 30-day mortality was not different (HR=0.98, 95% CI 0.82 to 1.16).We found that for the OSA group, comorbid airways disease but not cardiometabolic conditions increased the hazards of COVID-19-related outcomes, including mortality. CONCLUSION: In this large population-based study, we demonstrated that a recent diagnosis of OSA requiring treatment was associated with an increased hazard of testing positive for COVID-19 and serious COVID-19-related complications, particularly in those with co-existing chronic airways disease.

Quantifying COPD as a risk factor for cardiac disease in a primary prevention cohort.

BACKGROUND: Despite COPD being a risk factor for cardiovascular disease (CVD) and knowing that risk stratification for CVD primary prevention is important, little is known about the real-world risk of CVD among people with COPD with no history of CVD. This knowledge would inform CVD management for people with COPD. The current study aimed to examine the risk of major adverse cardiovascular events (MACE) (including acute myocardial infarction, stroke or cardiovascular death) in a large, complete real-world population with COPD without previous CVD. METHODS: We conducted a retrospective population cohort study using health administrative, medication, laboratory, electronic medical record and other data from Ontario, Canada. People without a history of CVD with and without physician-diagnosed COPD were followed between 2008 and 2016, and cardiac risk factors and comorbidities compared. Sequential cause-specific hazard models adjusting for these factors determined the risk of MACE in people with COPD. RESULTS: Among ∼5.8 million individuals in Ontario aged ≥40 years without CVD, 152 125 had COPD. After adjustment for cardiovascular risk factors, comorbidities and other variables, the rate of MACE was 25% higher in persons with COPD compared with those without COPD (hazard ratio 1.25, 95% CI 1.23-1.27). CONCLUSIONS: In a large real-world population without CVD, people with physician-diagnosed COPD were 25% more likely to have a major CVD event, after adjustment for CVD risk and other factors. This rate is comparable to the rate in people with diabetes and calls for more aggressive CVD primary prevention in the COPD population.

Eligibility criteria from pharmaceutical randomised controlled trials of idiopathic pulmonary fibrosis: a registry-based study.

BACKGROUND: Little is known about generalisability of randomised controlled trials (RCTs) for idiopathic pulmonary fibrosis (IPF). We evaluated eligibility criteria for phase III IPF RCTs to determine their representativeness in clinical registries, and calculated forced vital capacity (FVC) changes according to eligibility criteria. METHODS: Common eligibility criteria used in >60% of IPF RCTs were identified from a literature search and applied to patients with IPF from prospective Australian and Canadian registries. Additional pre-specified criteria of 6-min walk distance (6MWD) and different measures of preceding disease progression were also evaluated. Joint longitudinal-survival modelling was used to compare FVC decline according to eligibility for individual and composite criteria. RESULTS: Out of 990 patients with IPF, 527 (53%) met all common RCT eligibility criteria at the first clinic visit, including 343 with definite IPF and 184 with radiological probable usual interstitial pneumonia pattern without histological confirmation (i.e. provisional IPF). The percentages of eligible patients for landmark RCTs of nintedanib and pirfenidone were 19-50%. Adding 6MWD ≥150 m and different measures of preceding disease progression to the composite common criteria reduced the percentages of patients meeting eligibility to 52% (n=516) and 4-18% (n=12-61), respectively. Patients meeting the composite common criteria had less-rapid 1-year FVC decline than those who did not (-90 versus -103 mL, p=0.01). Definite IPF generally had more-rapid 1-year FVC decline compared to provisional IPF. CONCLUSIONS: Eligibility criteria of previous IPF RCTs have limited generalisability to clinical IPF populations, with FVC decline differing between eligible and ineligible populations.

Survival and health care costs after inpatient elective surgery: comparison of patients with and without chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is common among surgical patients, and patients with COPD have higher risk for complications and death within 30 days after surgery. We sought to describe the longer-term postoperative survival and costs of patients with COPD compared with those without COPD within 1 year after inpatient elective surgery. METHODS: In this retrospective population-based cohort study, we used linked health administrative databases to identify all patients undergoing inpatient elective surgery in Ontario, Canada, from 2005 to 2019. We ascertained COPD status using validated definitions. We followed participants for 1 year after surgery to evaluate survival and costs to the health system. We quantified the association of COPD with survival (Cox proportional hazards models) and costs (linear regression model with log-transformed costs) with partial adjustment (for sociodemographic factors and procedure type) and full adjustment (also adjusting for comorbidities). We assessed for effect modification by frailty, cancer and procedure type. RESULTS: We included 932 616 patients, of whom 170 482 (18%) had COPD. With respect to association with risk of death, COPD had a partially adjusted hazard ratio (HR) of 1.61 (95% confidence interval [CI] 1.58-1.64), and a fully adjusted HR of 1.26 (95% CI 1.24-1.29). With respect to impact on health system costs, COPD was associated with a partially adjusted relative increase of 13.1% (95% CI 12.7%-13.4%), and an increase of 4.6% (95% CI 4.3%-5.0%) with full adjustment. Frailty, cancer and procedure type (such as orthopedic and lower abdominal surgery) modified the association between COPD and outcomes. INTERPRETATION: Patients with COPD have decreased survival and increased costs in the year after surgery. Frailty, cancer and the type of surgical procedure modified associations between COPD and outcomes, and must be considered when risk-stratifying surgical patients with COPD.

Pandemic Effect on Healthcare Use and Death in Adults with Epilepsy: A Population Study.

OBJECTIVES: We conducted a population-based study using Ontario health administrative data to describe trends in healthcare utilization and mortality in adults with epilepsy during the first pandemic year (March 2020-March 2021) compared to historical data (2016-2019). We also investigated if changes in outpatient visits and diagnostic testing during the first pandemic year were associated with increased risk for hospitalizations, emergency department (ED) visits, or death. METHODS: Projected monthly visit rates (per 100,000 people) for outpatient visits, electroencephalography, magnetic resonance, computed tomography, all-cause ED visits, hospitalizations, and mortality were calculated based on historical data by fitting monthly time series autoregressive integrated moving-average models. Two-way interactions were calculated using Quasi-Poisson models. RESULTS: In adults with epilepsy during the first quarter of the pandemic, we demonstrated a reduction in all-cause outpatient visits, diagnostic testing, ED visits and hospitalizations, and a temporary increase in mortality (observed rates of 355.8 vs projected 308.8, 95% CI: 276.3-345.1). By the end of the year, outpatient visits increased (85,535.4 vs 76,620.6, 95% CI: 71,546.9-82,059.4), and most of the diagnostic test rates returned to the projected. The increase in the rate of all-cause mortality during the pandemic, compared to pre-pandemic, was greater during months with the lower frequency of diagnostic tests than months with higher frequency (interaction p-values <.0001). CONCLUSION: We described the impact of the pandemic on healthcare utilization and mortality in adults with epilepsy during the first year. We demonstrated that access to relevant diagnostic testing is likely important for this population while planning restrictions on non-urgent health services.

Development of Multivariable Prediction Models for the Identification of Patients Admitted to Hospital with an Exacerbation of COPD and the Prediction of Risk of Readmission: A Retrospective Cohort Study using Electronic Medical Record Data.

BACKGROUND: Approximately 20% of patients who are discharged from hospital for an acute exacerbation of COPD (AECOPD) are readmitted within 30 days. To reduce this, it is important both to identify all individuals admitted with AECOPD and to predict those who are at higher risk for readmission. OBJECTIVES: To develop two clinical prediction models using data available in electronic medical records: 1) identifying patients admitted with AECOPD and 2) predicting 30-day readmission in patients discharged after AECOPD. METHODS: Two datasets were created using all admissions to General Internal Medicine from 2012 to 2018 at two hospitals: one cohort to identify AECOPD and a second cohort to predict 30-day readmissions. We fit and internally validated models with four algorithms. RESULTS: Of the 64,609 admissions, 3,620 (5.6%) were diagnosed with an AECOPD. Of those discharged, 518 (15.4%) had a readmission to hospital within 30 days. For identification of patients with a diagnosis of an AECOPD, the top-performing models were LASSO and a four-variable regression model that consisted of specific medications ordered within the first 72 hours of admission. For 30-day readmission prediction, a two-variable regression model was the top performing model consisting of number of COPD admissions in the previous year and the number of non-COPD admissions in the previous year. CONCLUSION: We generated clinical prediction models to identify AECOPDs during hospitalization and to predict 30-day readmissions after an acute exacerbation from a dataset derived from available EMR data. Further work is needed to improve and externally validate these models.

Prevalence and characteristics of progressive fibrosing interstitial lung disease in a prospective registry.

BACKGROUND: Progressive fibrosing interstitial lung disease (PF-ILD) is characterised by progressive physiological, symptomatic and/or radiographic worsening. The real-world prevalence and characteristics of PF-ILD remain uncertain. METHODS: Patients were enrolled from the Canadian Registry for Pulmonary Fibrosis between 2015 and 2020. PF-ILD was defined as a relative forced vital capacity (FVC) decline ≥10%, death, lung transplantation or any two of: relative FVC decline ≥5% and <10%, worsening respiratory symptoms or worsening fibrosis on computed tomography of the chest, all within 24 months of diagnosis. Time-to-event analysis compared progression between key diagnostic subgroups. Characteristics associated with progression were determined by multivariable regression. RESULTS: Of 2746 patients with fibrotic ILD (mean±sd age 65±12 years; 51% female), 1376 (50%) met PF-ILD criteria in the first 24 months of follow-up. PF-ILD occurred in 427 (59%) patients with idiopathic pulmonary fibrosis (IPF), 125 (58%) with fibrotic hypersensitivity pneumonitis (HP), 281 (51%) with unclassifiable ILD (U-ILD) and 402 (45%) with connective tissue disease-associated ILD (CTD-ILD). Compared with IPF, time to progression was similar in patients with HP (hazard ratio (HR) 0.96, 95% CI 0.79-1.17), but was delayed in patients with U-ILD (HR 0.82, 95% CI 0.71-0.96) and CTD-ILD (HR 0.65, 95% CI 0.56-0.74). Background treatment varied across diagnostic subtypes, with 66% of IPF patients receiving antifibrotic therapy, while immunomodulatory therapy was utilised in 49%, 61% and 37% of patients with CHP, CTD-ILD and U-ILD, respectively. Increasing age, male sex, gastro-oesophageal reflux disease and lower baseline pulmonary function were independently associated with progression. CONCLUSIONS: Progression is common in patients with fibrotic ILD, and is similarly prevalent in HP and IPF. Routinely collected variables help identify patients at risk for progression and may guide therapeutic strategies.

Inhalational exposures in patients with fibrotic interstitial lung disease: Presentation, pulmonary function and survival in the Canadian Registry for Pulmonary Fibrosis.

BACKGROUND AND OBJECTIVE: Inhalational exposures are a known cause of interstitial lung disease (ILD), but little is understood about their prevalence across ILD subtypes and their relationship with pulmonary function and survival. METHODS: Patients with fibrotic ILD were identified from the multicentre Canadian Registry for Pulmonary Fibrosis. Patients completed questionnaires regarding ILD-related occupational and environmental exposures. The relationship between exposures and the outcomes of baseline age, gender, family history, pulmonary function and survival was analysed using linear and logistic regression models, linear mixed-effect regression models and survival analysis using multivariable Cox proportional hazards along with the log-rank test. RESULTS: There were 3820 patients included in this study, with 2385 (62%) having ILD-related inhalational exposure. Exposed patients were younger, particularly in the idiopathic pulmonary fibrosis subgroup. Inhalational exposure was associated with male gender (adjusted OR 1.46, 95% CI 1.28-1.68, p < 0.001) and family history of pulmonary fibrosis (adjusted OR 1.73, 95% CI 1.40-2.15, p < 0.001). Patients with any inhalational exposure had improved transplant-free survival (hazard ratio 0.81, 95% CI 0.71-0.92, p = 0.001); this effect persisted across diagnostic subtypes. The relationship between exposures and annual change in forced vital capacity varied by ILD subtype. CONCLUSION: Patients with fibrotic ILD report high prevalence of inhalational exposures across ILD subtypes. These exposures were associated with younger age at diagnosis, male gender and family history of pulmonary fibrosis. Identification of an inhalational exposure was associated with a survival benefit. These findings suggest that inhaled exposures may impact clinical outcomes in patients with ILD, and future work should characterize the mechanisms underlying these relationships.

Informing Healthcare Decisions with Observational Research Assessing Causal Effect. An Official American Thoracic Society Research Statement.

Rationale: Decisions in medicine are made on the basis of knowledge and reasoning, often in shared conversations with patients and families in consideration of clinical practice guideline recommendations, individual preferences, and individual goals. Observational studies can provide valuable knowledge to inform guidelines, decisions, and policy.Objectives: The American Thoracic Society (ATS) created a multidisciplinary ad hoc committee to develop a research statement to clarify the role of observational studies-alongside randomized controlled trials (RCTs)-in informing clinical decisions in pulmonary, critical care, and sleep medicine.Methods: The committee examined the strengths of observational studies assessing causal effects, how they complement RCTs, factors that impact observational study quality, perceptions of observational research, and, finally, the practicalities of incorporating observational research into ATS clinical practice guidelines.Measurements and Main Results: There are strengths and weakness of observational studies as well as RCTs. Observational studies can provide evidence in representative and diverse patient populations. Quality observational studies should be sought in the development of ATS clinical practice guidelines, and medical decision-making in general, when 1) no RCTs are identified or RCTs are appraised as being of low- or very low-quality (replacement); 2) RCTs are of moderate quality because of indirectness, imprecision, or inconsistency, and observational studies mitigate the reason that RCT evidence was downgraded (complementary); or 3) RCTs do not provide evidence for outcomes that a guideline committee considers essential for decision-making (e.g., rare or long-term outcomes; "sequential").Conclusions: Observational studies should be considered in developing clinical practice guidelines and in making clinical decisions.

Prescription Pathways from Initial Medication Use to Triple Therapy in Older COPD Patients: A Real-World Population Study.

BACKGROUND AND OBJECTIVE: Triple therapy with an inhaled corticosteroid (ICS), a long-acting ß2-agonist bronchodilator (LABA) and a long-acting muscarinic antagonist (LAMA) is recommended as step-up therapy for chronic obstructive pulmonary disease (COPD) patients who continue to have persistent symptoms and increased risk of exacerbation despite treatment with dual therapy. We sought to evaluate different treatment pathways through which COPD patients were escalated to triple therapy. METHODS: We used population health databases from Ontario, Canada to identify individuals aged 66 or older with COPD who started triple therapy between 2014 and 2017. Median time from diagnosis to triple therapy was estimated using the Kaplan-Meier method. We classified treatment pathways based on treatments received prior to triple therapy and evaluated whether pathways differed by exacerbation history, blood eosinophil counts or time period. RESULTS: Among 4108 COPD patients initiating triple therapy, only 41.2% had a COPD exacerbation in the year prior. The three most common pathways were triple therapy as initial treatment (32.5%), LAMA to triple therapy (29.8%), and ICS + LABA to triple therapy (15.4%). Median time from diagnosis to triple therapy was 362 days (95% confidence interval:331-393 days) overall, but 14 days (95% CI 12-17 days) in the triple therapy as initial treatment pathway. This pathway was least likely to contain patients with frequent or severe exacerbations (22.0% vs. 31.5%, p < 0.001) or with blood eosinophil counts ≥300 cells/µL (18.9% vs. 22.0%, p < 0.001). CONCLUSION: Real-world prescription of triple therapy often does not follow COPD guidelines in terms of disease severity and prior treatments attempted.

Morbidity and mortality associated with prescription cannabinoid drug use in COPD.

INTRODUCTION: Respiratory-related morbidity and mortality were evaluated in relation to incident prescription oral synthetic cannabinoid (nabilone, dronabinol) use among older adults with chronic obstructive pulmonary disease (COPD). METHODS: This was a retrospective, population-based, data-linkage cohort study, analysing health administrative data from Ontario, Canada, from 2006 to 2016. We identified individuals aged 66 years and older with COPD, using a highly specific, validated algorithm, excluding individuals with malignancy and those receiving palliative care (n=185 876 after exclusions). An equivalent number (2106 in each group) of new cannabinoid users (defined as individuals dispensed either nabilone or dronabinol, with no dispensing for either drug in the year previous) and controls (defined as new users of a non-cannabinoid drug) were matched on 36 relevant covariates, using propensity scoring methods. Cox proportional hazard regression was used. RESULTS: Rate of hospitalisation for COPD or pneumonia was not significantly different between new cannabinoid users and controls (HR 0.87; 95% CI 0.61-1.24). However, significantly higher rates of all-cause mortality occurred among new cannabinoid users compared with controls (HR 1.64; 95% CI 1.14-2.39). Individuals receiving higher-dose cannabinoids relative to controls were observed to experience both increased rates of hospitalisation for COPD and pneumonia (HR 2.78; 95% CI 1.17-7.09) and all-cause mortality (HR 3.31; 95% CI 1.30-9.51). CONCLUSIONS: New cannabinoid use was associated with elevated rates of adverse outcomes among older adults with COPD. Although further research is needed to confirm these observations, our findings should be considered in decisions to use cannabinoids among older adults with COPD.

Minimum important difference of the EQ-5D-5L and EQ-VAS in fibrotic interstitial lung disease.

RATIONALE: The European Quality of Life 5-Dimensions 5-Levels questionnaire (EQ-5D-5L) is a multidimensional patient-reported questionnaire that supports calculation of quality-adjusted life-years. Our objectives were to demonstrate feasibility of use and to calculate the minimum important difference (MID) of the EQ-5D-5L and its associated visual analogue scale (EQ-VAS) in patients with fibrotic interstitial lung disease (ILD). METHODS: Patients who completed the EQ-5D-5L were identified from the prospective multicentre CAnadian REgistry for Pulmonary Fibrosis. Validity, internal consistency and responsiveness of the EQ-5D-5L were assessed, followed by calculation of the MID for the EQ-5D-5L and EQ-VAS. Anchor-based methods used an unadjusted linear regression against pulmonary function tests (PFTs) and dyspnoea and other quality of life questionnaires. Distribution-based method used one-half SD and SE measurement (SEM) calculations. RESULTS: 1816 patients were analysed, including 472 (26%) with idiopathic pulmonary fibrosis. EQ-5D-5L scores were strongly correlated with the dyspnoea and other quality of life questionnaires and weakly associated with PFTs. The estimated MID for EQ-5D-5L ranged from 0.0050 to 0.054 and from 0.078 to 0.095 for the anchor-based and distribution-based methods, respectively. The MID for EQ-VAS ranged from 0.5 to 5.0 and from 8.0 to 9.7 for the anchor-based and distribution-based methods. Findings were similar across ILD subtypes, sex and age. CONCLUSION: We used a large and diverse cohort of patients with a variety of fibrotic ILD subtypes to suggest validity and MID of both the EQ-5D-5L and EQ-VAS. These findings will assist in designing future clinical trials and supporting cost-effectiveness analyses of potential treatments for patients with fibrotic ILD.

Validation and minimum important difference of the UCSD Shortness of Breath Questionnaire in fibrotic interstitial lung disease.

RATIONALE: The University of California, San Diego Shortness of Breath Questionnaire (UCSDSOBQ) is a frequently used domain-specific dyspnea questionnaire; however, there is little information available regarding its use and minimum important difference (MID) in fibrotic interstitial lung disease (ILD). We aimed to describe the key performance characteristics of the UCSDSOBQ in this population. METHODS: UCSDSOBQ scores and selected anchors were measured in 1933 patients from the prospective multi-center Canadian Registry for Pulmonary Fibrosis. Anchors included the St. George's Respiratory Questionnaire (SGRQ), European Quality of Life 5 Dimensions 5 Levels questionnaire (EQ-5D-5L) and EQ visual analogue scale (EQ-VAS), percent-predicted forced vital capacity (FVC%), diffusing capacity of the lung for carbon monoxide (DLCO%), and 6-min walk distance (6MWD). Concurrent validity, internal consistency, ceiling and floor effects, and responsiveness were assessed, followed by estimation of the MID by anchor-based (linear regression) and distribution-based methods (standard error of measurement). RESULTS: The UCSDSOBQ had a high level of internal consistency (Cronbach's alpha = 0.97), no obvious floor or ceiling effect, strong correlations with SGRQ, EQ-5D-5L, and EQ-VAS (|r| > 0.5), and moderate correlations with FVC%, DLCO%, and 6MWD (0.3 < |r| < 0.5). The MID estimate for UCSDSOBQ was 5 points (1-8) for the anchor-based method, and 4.5 points for the distribution-based method. CONCLUSION: This study demonstrates the validity of UCSDSOBQ in a large and heterogeneous population of patients with fibrotic ILD, and provides a robust MID estimate of 5-8 points.

Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline.

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.