Severe COPD Exacerbations Research Articles

Prompt initiation of triple therapy following hospitalization for a chronic obstructive pulmonary disease exacerbation in the United States: An analysis of the PRIMUS study.

BACKGROUND: Severe exacerbations requiring hospitalization contribute a substantial portion of the morbidity and costs of chronic obstructive pulmonary disease (COPD). Triple therapy (inhaled corticosteroid + long-acting β-agonist + long-acting muscarinic antagonist) is a recommended option for patients who experience recurrent COPD exacerbations or persistent symptoms. Few real-world studies have specifically examined the effect of prompt initiation of triple therapy, specifically among patients hospitalized for a COPD exacerbation. OBJECTIVE: To assess whether prompt initiation of triple therapy following a severe COPD exacerbation was associated with lower risk of subsequent exacerbations and lower health care use and costs and the effects of each 30-day delay of initiation. METHODS: Adults aged 40 years or older with COPD were identified in the Merative MarketScan Databases between January 1, 2010, and December 31, 2019, and were required to meet the following criteria: open or closed triple therapy (date of first closed prescription or last component of open=index treatment date), more than 1 inpatient admission with a primary COPD diagnosis (ie, severe exacerbation) in the prior 12 months (index exacerbation), 12 months of continuous enrollment before (baseline) and after (follow-up) index exacerbation, and absence of select respiratory diseases and cancer. Patients were stratified based on timing of open or closed triple therapy after the index exacerbation: prompt (≤30 days), delayed (31-180 days), or very delayed (181-365 days). Multivariable regression controlled for baseline characteristics (age, sex, insurance type, index year, comorbidities, prior treatment, and prior exacerbations) and estimated the odds of subsequent exacerbations, change in the number of exacerbations, and change in health care costs during 12-month follow-up associated with each 30-day delay of triple therapy initiation. RESULTS: A total of 6,772 patients met inclusion criteria (2,968 [43.8%] prompt, 1,998 [29.5%] delayed, and 1,806 [26.7%] very delayed). The adjusted odds of any exacerbation and a severe exacerbation during 12-month follow-up increased by 13% (odds ratio [95% CI]: 1.13 [1.11-1.15]) and 10% (1.10 [1.08-1.12]), respectively, for each 30-day delay in triple therapy initiation, and the mean number of exacerbations increased by 5.4% (95% CI = 4.7%-6.1%). There was a 3.0% increase (95% CI = 2.2%-3.8%) in mean all-cause costs and a 3.7% increase (95% CI = 2.9%-4.6%) in total COPD-related costs for each 30-day delay of triple therapy initiation. CONCLUSIONS: Longer delays in triple therapy initiation after a COPD hospitalization result in greater risk of subsequent exacerbations and higher health care resource use and costs. Adequate post-discharge follow-up care and earlier consideration of triple therapy may improve clinical and economic outcomes among patients with COPD. DISCLOSURES: This study was funded by AstraZeneca. Dr Evans is employed by Merative, formerly IBM Watson Health, and Mr Tkacz was employed by IBM Watson Health at the time of this study; Merative/IBM Watson Health received funding from AstraZeneca to conduct this study. Mr Pollack, Dr Staresinic, Dr Feigler, and Dr Patel are employed by AstraZeneca. Dr Touchette, Dr Portillo, and Dr Strange are paid consultants to AstraZeneca. Dr Strange also participates in research grants paid to the Medical University of South Carolina by AstraZeneca, CSA Medical, and Nuvaira, and is a consultant to GlaxoSmithKline, Morair, and PulManage regarding COPD.

Low-density lipoprotein cholesterol and risk of COPD: Copenhagen General Population Study.

Randomised controlled trials found that low-density lipoprotein (LDL) cholesterol-lowering statins increase lung function and possibly decrease rate of exacerbations in individuals with COPD. However, it is unknown whether high levels of LDL cholesterol are associated with increased susceptibility to COPD. We tested the hypothesis that high LDL cholesterol is associated with increased risk of COPD, severe COPD exacerbation and COPD-specific mortality. We examined 107 301 adults from the Copenhagen General Population Study. COPD outcomes were ascertained at baseline and prospectively through nationwide registries. In cross-sectional analysis, low LDL cholesterol was associated with increased risk of COPD (odds ratio for 1st versus 4th quartile: 1.07 (95% CI 1.01-1.14)). Prospectively, low LDL cholesterol was associated with increased risk of COPD exacerbations with hazard ratios of 1.43 (1.21-1.70) for 1st versus 4th quartile, 1.21 (1.03-1.43) for 2nd versus 4th quartile, and 1.01 (0.85-1.20) for 3rd versus 4th quartile of LDL cholesterol (p-value for trend=6×10-6). Finally, low LDL cholesterol was likewise associated with increased risk of COPD-specific mortality (log-rank test: p=0.0009). Sensitivity analyses with death as competing risk provided similar results. Low LDL cholesterol was associated with increased risks of severe COPD exacerbation and COPD-specific mortality in the Danish general population. As this is opposite of that observed in randomised controlled trials with statins, our findings might be a result of reverse causation indicating that individuals with severe phenotypes of COPD have lower plasma levels of LDL cholesterol due to wasting.

Respiratory and peripheral muscle strength influence recovery of exercise capacity after severe exacerbation of COPD? An observational prospective cohort study

BackgroundPatients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have decreased exercise tolerance, which may persist for months. In this context, little is known about the associations between muscle strength and recovery of exercise capacity. ObjectiveTo assess whether respiratory and peripheral muscle strength influence recovery of exercise capacity in patients hospitalized due to AECOPD. MethodsTwenty-seven AECOPD patients (aged 69 ± 7 years, 56% male) were included. The following assessments were performed within 24 to 72 h of hospital admission: (i) respiratory muscle strength, measured by maximal inspiratory and expiratory pressures (MIP and MEP); (ii) peripheral muscle strength, assessed by handgrip and quadriceps muscle strength; and (iii) exercise capacity, measured by 6-min walking distance (6MWD). The 6MWD was reassessed 30 days later to determine the recovery of exercise capacity. ResultsAfter 30 days, while 63% of the patients showed clinically important improvement in the 6MWD (recovery ≥ 30 m), 37% showed no change (recovery < 30 m). During hospital stay, the non-recovered group had lower quadriceps muscle strength compared to the recovered group (15 ± 5 vs. 22 ± 6 kgf; P = 0.006), with no significant difference for MIP, MEP and handgrip strength. Only quadriceps muscle strength was associated with recovery of exercise capacity (r = 0.56; P = 0.003). ConclusionAECOPD patients with quadriceps muscle weakness during hospitalization have poor recovery of exercise capacity after 30 days. This finding suggests the importance of early rehabilitation to improve quadriceps strength and accelerate functional recovery after AECOPD.

Esophageal Pressure Measurement in Acute Hypercapnic Respiratory Failure Due to Severe COPD Exacerbation Requiring NIV-A Pilot Safety Study.

Esophageal pressure (Pes) measurements could optimise ventilator parameters in acute respiratory failure (ARF) patients requiring noninvasive ventilation (NIV). Consequently, the objectives of our study were to evaluate the safety and accuracy of applying a Pes measuring protocol in ARF patients with AECOPD under NIV in our respiratory intermediate care unit (RICU). An observational cohort study was undertaken. The negative inspiratory swing of Pes (ΔPes) was measured: in an upright/supine position in the presence/absence of NIV at D1 (day of admission), D3 (3rd day of NIV), and DoD (day of discharge). A digital filter for artefact removal was developed. We included 15 patients. The maximum values for ∆Pes were recorded at admission (mean ∆Pes 23.2 cm H2O) in the supine position. ∆Pes decreased from D1 to D3 (p &lt; 0.05), the change being BMI-dependent (p &lt; 0.01). The addition of NIV decreased ∆Pes at D1 and D3 (p &lt; 0.01). The reduction of ∆Pes was more significant in the supine position at D1 (8.8 cm H2O, p &lt; 0.01). Under NIV, ∆Pes values remained higher in the supine versus upright position. Therefore, the measurement of Pes in AECOPD patients requiring NIV can be safely done in an RICU. Under NIV, ∆Pes reduction is most significant within the first 24 h of admission.

Factors associated with poor long-term adherence after completing a pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease.

Although pulmonary rehabilitation programmes (PRPs) benefit patients with chronic obstructive pulmonary disease (COPD), poor adherence to these programmes is common. This study aimed to analyse the factors associated with poor long-term adherence after completing a PRP. We conducted a retrospective study of 70 patients with COPD who performed an 8-week outpatient PRP that included 24 sessions of aerobic training, skeletal muscle resistance exercises, physiotherapy and COPD education. The study classified the patients into 2 groups: (1) long-term adherence and (2) long-term non-adherence to the PRP. We considered long-term non-adherence when the patient did not attend the 32 weeks follow-up visit after beginning the PRP. We measured the degree of dyspnoea, quality of life, physical activity, anxiety-depression status, submaximal exercise capacity and COPD exacerbations in both groups. The patients' median age was 69.6 [63.8-75.0] years, and 71.4% were men. The median forced expiratory volume in 1 second was 60.0 [47.7-68.0] % of that predicted. We observed total COPD exacerbations and severe COPD exacerbations in the last year in 32 (45.7%) and 22 (31.4%) patients, respectively. Dyspnoea, physical activity and quality of life significantly improved after completing the PRP. Long-term non-adherence to the PRP was observed in 32 (45.7%) patients. In the single regression model, severe COPD exacerbations (p = 0.04) and dyspnoea (p = 0.03) were associated with long-term non-adherence to the PRP. In the multiple regression model, only severe COPD exacerbations remained as an associated factor (OR 2.7; 95% CI 1.1-8,1; p = 0.04). Approximately half of patients who complete PRPs present long-term non-adherence to the programme. Severe COPD exacerbations are associated with long-term non-adherence.

Abstract 15304: Apical Ballooning Syndrome in the Setting of Severe Chronic Obstructive Pulmonary Disease Exacerbation

Apical ballooning syndrome (ABS), also known as Takotsubo cardiomyopathy, is a form of acute dilated cardiomyopathy associated with excessive catecholamine release. A 74-year-old female, chronic smoker with previously diagnosis of obstructive lung disease presented in the emergency department with severe shortness of breath and increase sputum production for the last 24hr. The patient was diagnosed with severe COPD exacerbation and received multiple doses of albuterol, methylprednisolone, ipratropium bromide/albuterol, and azithromycin. Despite this, the patient remained tachypneic and tachycardic with signs of impending respiratory failure. She was transferred to the ICU and intubated. After intubation, the patient received a continuous albuterol nebulizer, methylprednisolone, and ceftriaxone. A few hours later, the patient complained of chest pain, and EKG was done showing T wave inversion in lateral leads, troponin levels were 1.08 ng/mL (ULN 0.12ng/mL), and 2D Echo showed EF 50-55%, apical ballooning with dyskinesia, and inferior wall hypokinesis. Left heart catheterization showed non-obstructive coronary artery disease with 50% stenosis on the left anterior descending artery and distal ostial artery. Based on the previously recommended criteria, the diagnosis of the ABS was made. The patient had resolution of symptoms and echocardiogram findings after follow up. Although albuterol acts mainly on beta-2 receptors, cross-activation of beta-1 receptors can potentially lead to tachycardia. Previous case reports also support that excessive albuterol use in cases of asthma and COPD exacerbation may lead to ABS. This case may raise awareness that the extensive use of albuterol could have dramatic effects. Early switch to beta-2 agonist with higher specificity such as levalbuterol could be a reasonable approach in patients with severe COPD exacerbation.

BURDEN OF ILLNESS IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO COPD IN US ADMINISTRATIVE CLAIMS DATA

BURDEN OF ILLNESS IN PATIENTS WITH PULMONARY HYPERTENSION DUE TO COPD IN US ADMINISTRATIVE CLAIMS DATA

A detailed analysis of possible efficacy signals of NTHi-Mcat vaccine against severe COPD exacerbations in a previously reported randomised phase 2b trial

BackgroundAn investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation. MethodsPatients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2–4), 40–80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses. ResultsOf 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6–12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001). ConclusionResults suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial. Trial registrationClinicalTrials.gov, NCT03281876.

Two-Year Mortality Following a Severe COPD Exacerbation in Bulgarian Patients

Abstract Two-year mortality in patients with COPD is expected to be between 10% and 49% depending on the investigated subgroup and specific patients’ characteristics. Aim: To assess the two-year mortality in COPD patients following hospitalization for severe exacerbation and to describe the prognostic value of comorbidities and specific patients’ characteristics. Materials and methods: We included 152 consecutive patients hospitalized for COPD exacerbation and signing informed consent. The Metabolic syndrome (MS), diabetes mellitus (DM), and hypovitaminosis D were diagnosed according to international guidelines. Demographic parameters (age, sex, smoking status, and the number of pack-years) were recorded. Quality of life was examined using CAT and mMRC questionnaires. The lung function was assessed by spirometry. Two-year mortality was determined according to data extracted from the national death register. Results: Two-year mortality rate was 11.8%. The investigated comorbidities – DM, MS, arterial hyper-tension (AH) and vitamin D status were no predictors of the two-year mortality. Mortality was increased in patients with mMRC ≥ 2 (17.2 vs. 1.9%, p = 0.005) and CAT score ≥ 10 (14.2 vs. 0%, p = 0.045). Severe exacerbation during the previous year was a risk factor for the registered two-year mortality (17.5% vs 5.6%, p = 0.021). The two-year mortality was increased in the group with FEV1 &lt; 50%, compared to FEV1 &gt; 50% (18.0 vs. 7.7%, p = 0.049). Cox regression analysis showed a 3.0% increase in the mortality rate for each 1% decrease in FEV1, 6.2% for each 1% decrease in PEF, 7.8% for one year of increasing age, 4% for 1% decrease in the FEV1/FVC ratio and 7.1% for each 1 point increase of CAT (all p-values &lt; 0.05). Conclusions: The two-year mortality of COPD patients following a severe exacerbation was relatively low. Chronological age, FEV1, history for severe exacerbation during the previous year, reduced quality of life, and low BMI were all associated with increased mortality. Disease Grade C, mMRC &lt; 2, and CAT score &lt; 10 were associated with a favourable prognosis.

Prevalence and Impact of Comorbidities in Individuals with Chronic Obstructive Pulmonary Disease: A Systematic Review

This study aimed to describe the prevalence of comorbidities associated with chronic obstructive pulmonary disease (COPD) and their relation with relevant outcomes. A systematic review based on the PRISMA methodology was performed from January 2020 until July 2021. The MEDLINE, Lilacs, and Scielo databases were searched to identify studies related to COPD and its comorbidities. Observational studies on the prevalence of comorbidities in COPD patients and costs with health estimates, reduced quality of life, and mortality were included. Studies that were restricted to one or more COPD pain assessments and only specific comorbidities such as osteoporosis, bronchitis, and asthma were excluded. The initial search identified 1,409 studies and after applying the inclusion and exclusion criteria, 20 studies were finally selected for analysis (comprising data from 447,459 COPD subjects). The most frequent COPD comorbidities were: hypertension (range, 17%–64.7%), coronary artery disease (19.9%–47.8%), diabetes (10.2%–45%), osteoarthritis (18%–43.8%), psychiatric conditions (12.1%–33%), and asthma (14.7%–32.5%). Several comorbidities had an impact on the frequency and severity of COPD exacerbations, quality of life, and mortality risk, in particular malignancies, coronary artery disease, chronic heart failure, and cardiac arrhythmias. Comorbidities, especially cardiovascular diseases and diabetes, are frequent in COPD patients, and some of them are associated with higher mortality.

Diaphragmatic Movement at Rest and After Exertion: A Non-Invasive and Easy to Obtain Prognostic Marker in COPD.

IntroductionDiaphragmatic dysfunction is common in patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the prognostic significance of impaired diaphragmatic movement at rest and after exercise.MethodsThis was a prospective study of patients with stable COPD. Diaphragmatic movements were examined at rest and after a 6-minute walking test (6MWT) with a convex transducer with a frequency of 3.5-5-7.5 MHz. Maximal movement of the diaphragm was measured in both right and left diaphragm, and the side with higher amplitude was selected for further analysis. Measurements obtained were evaluated for their prognostic value for a composite endpoint of moderate and severe COPD exacerbations and death in 1 year time period was assessed. In addition, postbronchodilator spirometry, symptoms, quality of life, and demographic and clinical information were collected.ResultsA total of 96 patients were analyzed (62.5% male, mean age 65.1 years (standard deviation (SD): 8.1), mean FEV1 (% predicted): 55.8%, SD: 18.3%, mean CAT: 15.6 units, SD: 9.2). Sixty-four patients (67%) presented the composite endpoint. In the multivariate Cox analysis, FVC (HR = 0.944, p = 0.005), CAT score (HR = 1.133, p = 0.011), previous severe exacerbations (HR = 5.446, p = 0.004) and diaphragmatic movement at rest (HR = 0.932, p = 0.033) were found to be predictors of the composite endpoint. This model correctly classified 86.5% (83/96) of the patients.ConclusionNon-invasive assessment of diaphragmatic movement by ultrasound measurement both at rest and after exercise could contribute to the assessment of disease severity and prognosis of COPD.

The Impact of Oxygen Pulse and Its Curve Patterns on Male Patients with Heart Failure, Chronic Obstructive Pulmonary Disease, and Healthy Controls-Ejection Fractions, Related Factors and Outcomes.

Oxygen pulse (O2P) is a function of stroke volume and cellular oxygen extraction and O2P curve pattern (O2PCP) can provide continuous measurements of O2P. However, measurements of these two components are difficult during incremental maximum exercise. As cardiac function is evaluated using ejection fraction (EF) according to the guidelines and EF can be obtained using first-pass radionuclide ventriculography, the aim of this study was to investigate associations of O2P%predicted and O2PCP with EF in patients with heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) and chronic obstructive pulmonary disease (COPD), and also in normal controls. This was a prospective observational cross-sectional study. Correlations of resting left ventricular EF, dynamic right and left ventricular EFs and outcomes with O2P% and O2PCP across the three participant groups were analyzed. A total of 237 male subjects were screened and 90 were enrolled (27 with HFrEF/HFmrEF, 30 with COPD and 33 normal controls). O2P% and the proportions of the three types of O2PCP were similar across the three groups. O2P% reflected dynamic right and left ventricular EFs in the control and HFrEF/HFmrEF groups, but did not reflect resting left ventricular EF in all participants. O2PCP did not reflect resting or dynamic ventricular EFs in any of the subjects. A decrease in O2PCP was significantly related to nonfatal cardiac events in the HFrEF/HFmrEF group (log rank test, p = 0.01), whereas O2P% and O2PCP did not predict severe acute exacerbations of COPD. The findings of this study may clarify the utility of O2P and O2PCP, and may contribute to the currently used interpretation algorithm and the strategy for managing patients, especially those with HFrEF/HFmrEF. (Trial registration number NCT05189301.)

Benefit of Prompt versus Delayed Use of Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Following a COPD Exacerbation.

PurposeTriple therapy (TT; inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β2-agonist) is recommended for patients with chronic obstructive pulmonary disease (COPD) at risk of exacerbation, although the optimum timing of TT initiation remains unclear. This study evaluated the impact of prompt versus delayed initiation of single-inhaler TT (fluticasone furoate, umeclidinium, and vilanterol [FF/UMEC/VI]) following a COPD exacerbation.Patients and MethodsThis retrospective cohort study used data from the IQVIA PharMetrics® Plus database. Patients initiating FF/UMEC/VI following a COPD exacerbation between September 18, 2017 and September 30, 2019 (exacerbation = index date) were categorized as prompt (within 30 days of index) or delayed (31–180 days after index) FF/UMEC/VI initiators. Patients were aged ≥40 years at index, had ≥12 months’ continuous health insurance coverage before index (baseline), and ≥6 months’ coverage after index (follow-up). Patients with a COPD exacerbation or claim for FF/UMEC/VI during baseline were excluded. Inverse probability weighting was used to adjust for differences in baseline characteristics between cohorts. Exacerbations (overall, moderate, and severe), healthcare costs, and readmissions were evaluated during follow-up.ResultsA total of 1904 patients (prompt: 529; delayed: 1375) were included. After weighting, baseline characteristics were well balanced between cohorts. Patients in the prompt cohort had significantly lower rates per person-year (PPY) of overall (0.98 vs 1.23; rate ratio [RR] [95% CI] = 0.79 [0.65–0.94], p = 0.004), moderate (0.86 vs 1.03; RR [95% CI] = 0.84 [0.69–0.99], p = 0.038), and severe (0.11 vs 0.20; RR [95% CI] = 0.57 [0.37–0.79], p = 0.002) exacerbations, compared with delayed initiators. Mean all-cause and COPD-related healthcare costs were significantly lower among prompt initiators (all-cause: $26,107 vs $32,400 PPY, p = 0.014; COPD-related: $12,694 vs $17,640 PPY, p = 0.002).ConclusionPrompt initiation of FF/UMEC/VI following a moderate or severe COPD exacerbation was associated with significant reductions in exacerbations and healthcare costs relative to delayed initiation.

Automatically Explaining Machine Learning Predictions on Severe Chronic Obstructive Pulmonary Disease Exacerbations: Retrospective Cohort Study.

BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of death and places a heavy burden on health care. To optimize the allocation of precious preventive care management resources and improve the outcomes for high-risk patients with COPD, we recently built the most accurate model to date to predict severe COPD exacerbations, which need inpatient stays or emergency department visits, in the following 12 months. Our model is a machine learning model. As is the case with most machine learning models, our model does not explain its predictions, forming a barrier for clinical use. Previously, we designed a method to automatically provide rule-type explanations for machine learning predictions and suggest tailored interventions with no loss of model performance. This method has been tested before for asthma outcome prediction but not for COPD outcome prediction.ObjectiveThis study aims to assess the generalizability of our automatic explanation method for predicting severe COPD exacerbations.MethodsThe patient cohort included all patients with COPD who visited the University of Washington Medicine facilities between 2011 and 2019. In a secondary analysis of 43,576 data instances, we used our formerly developed automatic explanation method to automatically explain our model’s predictions and suggest tailored interventions.ResultsOur method explained the predictions for 97.1% (100/103) of the patients with COPD whom our model correctly predicted to have severe COPD exacerbations in the following 12 months and the predictions for 73.6% (134/182) of the patients with COPD who had ≥1 severe COPD exacerbation in the following 12 months.ConclusionsOur automatic explanation method worked well for predicting severe COPD exacerbations. After further improving our method, we hope to use it to facilitate future clinical use of our model.International Registered Report Identifier (IRRID)RR2-10.2196/13783

The HUNT study: Association of comorbidity clusters with long-term survival and incidence of exacerbation in a population-based Norwegian COPD cohort.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease often viewed as part of a multimorbidity complex. There is a need for better phenotyping of the disease, characterization of its interplay with other comorbidities and its association with long-term outcomes. This study aims to examine how clusters of comorbidities are associated with severe exacerbations and mortality in COPD. Participants with potential COPD were recruited from the second (1995-1997) and third (2006-2008) survey of the HUNT Study and followed up until April 2020. Ten objectively identified comorbidities were clustered using self-organizing maps. Severe COPD exacerbations requiring hospitalization were assessed using hospital data. All-cause mortality was collected from national registries. Multivariable Cox regression was used to calculate hazard ratios (HRs) with 95% CIs for the association between comorbidity clusters and all-cause mortality. Poisson regression was used to calculate incidence rate ratios (IRRs) with 95% CI for the cumulative number of severe exacerbations for each cluster. Five distinct clusters were identified, including 'less comorbidity', 'psychological', 'cardiovascular', 'metabolic' and 'cachectic' clusters. Using the less comorbidity cluster as reference, the psychological and cachectic clusters were associated with all-cause mortality (HR 1.23 [1.04-1.45] and HR 1.83 [1.52-2.20], adjusted for age and sex). The same clusters also had increased risk of exacerbations (unadjusted IRR of 1.24 [95% CI 1.04-1.48] and 1.50 [95% CI 1.23-1.83], respectively). During 25 years of follow-up, individuals in the psychological and cachectic clusters had increased mortality. Furthermore, these clusters were associated with increased risk of severe COPD exacerbations.

Saliva as a non-invasive specimen for COPD assessment

BackgroundPeople with COPD have been reported to bear a distinct airway microbiota from healthy individuals based on bronchoalveolar lavage (BAL) and sputum samples. Unfortunately, the collection of these samples involves relatively invasive procedures and is resource-demanding, limiting its regular use. Non-invasive samples from the upper airways could constitute an interesting alternative, but its relationship with COPD is still underexplored. We examined the merits of saliva to identify the typical profile of COPD oral bacteria and test its association with the disease.MethodsOutpatients with COPD and age-sex matched healthy controls were recruited and characterised based on clinical parameters and 16S rRNA profiling of oral bacteria. A clustering analysis based on patients’ oral bacteria beta-diversity and logistic regressions were performed to evaluate the association between oral bacteria composition and COPD.Results128 individuals participated (70 patients and 58 controls). Differential abundance analyses showed differences in patients comparable to the ones previously observed in samples from the lower respiratory tract, i.e., an increase in Proteobacteria (particularly Haemophilus) and loss of microbiota diversity. An unsupervised clustering analysis separated patients in two groups based on microbiota composition differing significantly in the frequency of patients hospitalized due to severe acute exacerbation of COPD (AECOPD) and in the frequency of GOLD D patients. Furthermore, a low frequency of Prevotella was associated with a significantly higher risk of recent severe AECOPD and of being GOLD D.ConclusionSalivary bacteria showed an association with COPD, particularly with severe exacerbations, supporting the use of this non-invasive specimen for future studies of heterogeneous respiratory diseases like COPD.

No evidence of harmful effects of steroids in severe exacerbations of COPD associated with influenza.

PurposeCOPD has large impact on patient morbidity and mortality worldwide. Acute exacerbations (AECOPD) are mostly triggered by respiratory infections including influenza. While corticosteroids are strongly recommended in AECOPD, they are potentially harmful during influenza. We aimed to evaluate if steroid treatment for AECOPD due to influenza may worsen outcomes.MethodsA retrospective analysis of a Swiss nation-wide hospitalization database was conducted identifying all AECOPD hospitalisations between 2012 and 2017. In separate analyses, outcomes concerning length-of-stay (LOS), in-hospital mortality, rehospitalisation rate, empyema and aspergillosis were compared between AECOPD during and outside influenza season; AECOPD with and without laboratory-confirmed influenza; and AECOPD plus pneumonia with and without laboratory-confirmed influenza.ResultsPatients hospitalized for AECOPD during influenza season showed shorter LOS (11.3 vs. 11.6 day, p < 0.001) but higher rehospitalisation rates (33 vs 31%, p < 0.001) compared to those hospitalized outside influenza season. Patients with confirmed influenza infection had lower in-hospital mortality (3.3 vs. 5.5%, p = 0.010) and rehospitalisation rates (29 vs. 37%, p < 0.001) than those without confirmed influenza.ConclusionUsing different indicators for influenza as the likely cause of AECOPD, we found no consistent evidence of worse outcomes of AECOPD due to influenza for hospitalized patients. Assuming that most of these patients received corticosteroids, as it is accepted standard of care in Switzerland, this study gives no evidence to change the current practice of using corticosteroids for hospitalized AECOPD independent of the influenza status.Supplementary InformationThe online version contains supplementary material available at 10.1007/s15010-021-01743-1.

Developing a Machine Learning Model to Predict Severe Chronic Obstructive Pulmonary Disease Exacerbations: Retrospective Cohort Study

BackgroundChronic obstructive pulmonary disease (COPD) poses a large burden on health care. Severe COPD exacerbations require emergency department visits or inpatient stays, often cause an irreversible decline in lung function and health status, and account for 90.3% of the total medical cost related to COPD. Many severe COPD exacerbations are deemed preventable with appropriate outpatient care. Current models for predicting severe COPD exacerbations lack accuracy, making it difficult to effectively target patients at high risk for preventive care management to reduce severe COPD exacerbations and improve outcomes.ObjectiveThe aim of this study is to develop a more accurate model to predict severe COPD exacerbations.MethodsWe examined all patients with COPD who visited the University of Washington Medicine facilities between 2011 and 2019 and identified 278 candidate features. By performing secondary analysis on 43,576 University of Washington Medicine data instances from 2011 to 2019, we created a machine learning model to predict severe COPD exacerbations in the next year for patients with COPD.ResultsThe final model had an area under the receiver operating characteristic curve of 0.866. When using the top 9.99% (752/7529) of the patients with the largest predicted risk to set the cutoff threshold for binary classification, the model gained an accuracy of 90.33% (6801/7529), a sensitivity of 56.6% (103/182), and a specificity of 91.17% (6698/7347).ConclusionsOur model provided a more accurate prediction of severe COPD exacerbations in the next year compared with prior published models. After further improvement of its performance measures (eg, by adding features extracted from clinical notes), our model could be used in a decision support tool to guide the identification of patients with COPD and at high risk for care management to improve outcomes.International Registered Report Identifier (IRRID)RR2-10.2196/13783

Study of hypogammaglobulinemia in patients with chronic obstructive pulmonary disease

Background Chronic obstructive pulmonary disease (COPD) is considered the third leading cause of death worldwide. Severe acute exacerbations of COPD are accompanied by increased number of hospital admissions, decreased lung function tests, decreased life quality, increased risk of recurrent hospital admissions, and decreased survival. Aim To assess the deficiency of immunoglobulin G (IgG) subclasses in patients with COPD. Patients and methodology The current research evaluated 120 patients admitted for COPD. The study included three groups: group 1 included 40 patients with acute exacerbation of COPD, group 2 included 40 patients with stable COPD, and group 3 included 40 age-matched controls. All of the study samples were obtained from all patients who participated in this study. The serum levels of IgG subclasses were measured using binding site IgG subclasses (IgG1–4). Results There were statistically significant differences among the three groups regarding BMI, smoking, and comorbidities. Moreover, there was a statistically significant difference among the three groups regarding white blood cell, lymphocyte%, and neutrophil%. In addition, there was a statistically significant difference among the three groups in the present study regarding respiratory function tests. Immunoglobulin levels (IgG) among the studied groups were statistically different. Moreover, we noticed a statistically significant positive relation among IgG1, IgG2, and BMI. Conclusion The current results denoted that IgG1 could be more sensitive, specific, and accurate than IgG2, IgG3, and IgG4 in predicting the status among patients with acute exacerbation of COPD.

Treatment patterns and cost of exacerbations in patients with chronic obstructive pulmonary disease using multiple inhaler triple therapy in South Korea

BackgroundMultiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed.MethodsThis was a retrospective cohort study using the South Korea National Health Insurance database (2014–2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months’ data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW).ResultsAmong 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75–0.78); mean PPPY total healthcare costs were 2093 USD.ConclusionsPatients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs.