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Patients with COPD and comorbid depression/anxiety are at risk of reduced health status. This study aimed to assess health status in COPD patients with depression/anxiety, the occurrence of severely reduced health status in this group, and to investigate associations between severely reduced health status and patient-related clinical factors. This cross-sectional study included 2245 randomly selected COPD patients from primary care and hospital outpatient clinics in Sweden. The COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ) were used to assess health status. Severely reduced health status was defined as CAT >= 20 or CCQ >= 2. The 524 patients (23.3%) who reported depression/anxiety had higher mean CAT scores (18.3 vs. 15.2, p < 0.001) and CCQ scores (2.37 vs. 1.83, p < 0.001) than patients without depression/anxiety. In this group, 48% had CAT >= 20 and 57% had CCQ >= 2. In patients with depression/anxiety, factors associated with CAT >= 20 were: onset of COPD symptoms before 60 years of age (OR = 2.62 [95% CI 1.37-5.04]), frequent symptoms of depression in the previous three months (2.59 [1.55-4.30]), one or more COPD exacerbations in the previous six months (2.37 [1.41-4.00]) and physical inactivity (1.89 [1.11-3.22]). Apart from physical inactivity, factors associated with CCQ >= 2 were the same as for CAT >= 20. Approximately half of the COPD patients with comorbid depression/anxiety reported severely reduced health status. Exacerbations, frequent depressive symptoms and physical inactivity were factors associated with severely reduced health status, and constitute important treatable and preventable traits of COPD.

Whether COPD should be diagnosed using the lower limit of normal (LLN) or a fixed FEV₁/FVC ratio <0.70 (FR) is debated. We compared symptom and disease burden in COPD patients with FEV₁/FVC below both thresholds (FR + /LLN + ) versus those between them (FR + /LLN-). This cohort study included 572 COPD patients from primary and secondary care in the central Swedish regions of Dalarna, Gävleborg, and Uppsala. FR + /LLN + COPD patients with FEV₁ ≥ 60% predicted (n = 194) was compared to FR + /LLN- COPD patients (n = 85) in order to have similar FEV₁ levels in both groups. The symptom burden was assessed using the modified British Medical Research Council scale of dyspnoea (mMRC), the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ). The disease burden was assessed by exacerbations and hospital admissions over the subsequent three years. The 279 studied patients (57% females) had a mean age of 68.2 years and a mean FEV₁% predicted of 73.0%. The FR + /LLN+ group had comparable clinical characteristics to the FR + /LLN- group regarding FEV₁% predicted (72.5 vs 74.2%), use of inhaled medicines (76.3 vs 76.5%), and previous exacerbations (23.2 vs 18.8%), all p-values > 0.05. Moreover, comparable prevalence of exacerbations and hospital admissions were found during the subsequent three years (31.7 vs 37.7%, and 4.8 vs 2.6%, respectively, all p-values > 0.05). Symptom burden was comparable for mMRC and CCQ, but the FR + /LLN- group had a higher CAT score than the FR + /LLN+ group (10.6 vs 12.6, p = 0.038), a finding also confirmed in adjusted analyses. FR + /LLN+ and FR + /LLN- COPD patients had relatively comparable symptom and disease burden, suggesting that not meeting the LLN criteria does not indicate a milder disease in clinically diagnosed COPD with comparable FEV₁.

BACKGROUND AND AIM: Patients with COPD and concurrent depression and/or anxiety are known to have an increased risk of exacerbations, morbidity, mortality, and deteriorated quality of life. Early detection of depression/anxiety may enable early interventions. The aims of this study were to describe the occurrence of depression and anxiety in primary care patients with COPD in Sweden, and to investigate age and gender differences together with other clinical factors associated with this comorbidity.

METHODS: A cross-sectional study was performed on a cohort of patients with doctor's diagnoses of COPD. Patients were randomly selected based on the patients' contact with 98 primary healthcare centers and 13 hospitals in Sweden in 2014. Information about self-reported depression/anxiety, patient characteristics, symptoms, and comorbidity, were collected using patient self-completion questionnaires. Lung function data were extracted from medical records.

RESULTS: Of the 2245 patients recruited, 23% (n = 524) reported depression/anxiety, 29% in women and 16% in men (p <0.001). Factors associated with depression/anxiety were being a woman (OR = 2.06 [95% CI 1.56-2.72]), current smoking (1.83 [1.37-2.43]), comorbid asthma (1.77 [1.32-2.37]), dyspnea (the modified Medical Research Council dyspnea scale ≥2 points) (1.58 [1.17-2.13]) and age <65 years (1.57 [1.17-2.10]). The youngest age groups had the highest proportions of patients with depression/anxiety.

CONCLUSIONS: Healthcare professionals need to be particularly aware of depression/anxiety in patients with COPD who are younger, women, current smokers, have comorbid asthma, or dyspnea.

Objective We aimed to examine the variability of chronic obstructive pulmonary disease (COPD) exacerbations and mortality, between primary healthcare centres, and their associations with comorbid diseases and body mass index, during an 8-year follow-up.Design This was a cohort study using multilevel modelling with follow-up from 2014 to 2022. Data came from questionnaires in 2014 and 2022 and medical record reviews between 2004 and 2014. The main outcomes were exacerbations in 2022 and mortality by 2022. Exacerbations were defined as any emergency visit, and/or use of oral steroids or antibiotics due to worsening of COPD symptoms during the previous 6 months.Setting The PRAXIS study included patients at 76 primary healthcare centres in central Sweden.Participants Primary care patients aged <= 75 years and with a diagnosis of COPD in their medical records between 2007 and 2010 were included in 2014 (n=1163) and followed up in 2022 (n=906). There were no other exclusion criteria.Results The 809 patients with complete data attended 70 primary care centres. Multilevel multinomial regression estimated risks of exacerbations and mortality, calculating relative risk ratios (RRRs) with 95% CIs. The intraclass correlation coefficient (ICC) quantified the proportion of variance attributed to variability between centres. The ICC was 0.024, indicating 2.4% of the variation was explained by differences between centres. Patients with a history of depression in 2014 had an increased risk of subsequent exacerbations (RRR 1.95, 95% CI 1.13 to 3.39). For mortality, there were associations with history of anxiety, RRR 3.71 (95% CI 2.06 to 6.87), or cardiovascular disease, especially chronic heart failure, RRR 2.69 (95% CI 1.36 to 5.33). Body mass index had a U-shaped association with mortality.Conclusions The variability between centres was small and patient factors appear to be of more importance for COPD exacerbations and mortality than differences between these primary care settings. As expected, pre-existing cardiovascular disease is associated with future excess mortality risk, but, notably, anxiety may also be an important risk factor. Individualised care and management of comorbidity is thus essential among patients in primary care with COPD.

Background

Comorbid conditions and breathlessness are associated with poor outcomes in chronic obstructive pulmonary disease (COPD). We evaluated the associations of comorbid heart disease and depression/anxiety with breathlessness in daily life among people with COPD.

Methods

Cross-sectional analysis from the PRAXIS cohort in central Sweden. Data on patient characteristics and the modified Medical Research Council (mMRC) and Dyspnea-12 breathlessness instruments (D-12) were obtained from questionnaires in 2022. Lung function data were collected from record review. Outcome variables were clinically significant breathlessness defined as mMRC≥2 and D-12 total (>2.7), physical (>1.4) and affective (>1.2) scores above published minimal clinical important differences. Associations of heart disease and depression/anxiety with each outcome were analyzed using multivariable Poisson regression adjusted for relevant confounders.

Results

In 522 included patients, mMRC ≥2 was present in 59 % and increased D-12 total, physical and affective domain scores in 69 %, 74 %, and 50 %, respectively. Heart disease was independently associated with mMRC (relative risk ratio [95 % confidence interval] 1.34 [1.17–1.53]), D12 physical domain (1.12[1.02–1.24]) and D-12 affective domain (1.20[1.02–1.42]). Depression/anxiety was independently associated with increased D-12 affective domain (1.25[1.04–1.49]). In addition, previous exacerbations and GOLD stage 3–4 were associated with mMRC and D-12, respectively.

Conclusion

In COPD, comorbid heart disease is associated with both activity-related breathlessness and with physical and affective domains of breathlessness while depression/anxiety is associated with the affective domain of breathlessness. As the influence of different dimensions of breathlessness may differ according to comorbidity the D-12 instrument adds more information when assessing breathlessness in patients with COPD.

Background: In 2017, Burgel and colleagues developed an algorithm to identify clinical phenotypes that predict mortality in COPD. Our study aimed to 1) investigate whether the phenotypes can predict acute exacerbations of COPD (AECOPD) and 2) validate their ability to predict mortality.

Methods: The Tools Identifying Exacerbations (TIE) cohort study recruited participants with spirometry-verified COPD from primary and secondary care in three Swedish regions. Participants were allocated to phenotypes 1–5 using the previously developed algorithm containing comorbidities (heart failure, coronary artery disease, hypertension, and/or diabetes), dyspnoea, age, forced expiratory volume in 1 s (FEV1), and body mass index (BMI). Data on AECOPDs and deaths during the three-year follow-up were collected from medical records and analysed with Cox proportional hazards regressions. Harrel's C-index was used to assess the models' discriminative ability.

Results: Among the 566 participants, 59 % were female, and the mean ± SD FEV1 was 57 ± 18 % of predicted. The hazard ratios (HRs) [95 % CI] for time to AECOPD were 3.04 [1.93–4.79], 2.38 [1.54–3.66], and 3.52 [1.73–7.15] in phenotypes 1, 2, and 4 compared with 5 (C-index = 0.61). When AECOPD history was used to predict future AECOPD the C-index was 0.65.The HRs [95 % CI] for mortality were 8.24 [1.93–35.3], 6.26 [1.40–28.0], and 16.7 [3.25–86.3] in phenotypes 1, 3, and 4 compared to 5 (C-index = 0.68). For AECOPD history, the C-index was 0.55.

Conclusion: Clinical COPD phenotypes based on comorbidities, dyspnoea, age, FEV1, and BMI predict AECOPDs but do not perform better than AECOPD history. However, they perform better than AECOPD history in predicting mortality.

The non-invasive biological marker exhaled nitric oxide (FENO) is increasingly used in asthma, but its clinical role in COPD is less established. FENO has been reported to be both high and low outside the COPD exacerbation period.

The study aimed to follow FENO values over two years during stable conditions in a cohort of COPD subjects participating in the TIE-study (Tools Identifying Exacerbation). The follow-up study included 353 subjects who attended three visits one year apart. The subjects that were ex-smokers (n = 265) had higher FENO,50 values (median and IQR) compared with current smokers (n = 88), at inclusion 15 (10, 24) versus 9 (7, 15) ppb, after one year 15 (10, 24) versus 10 (7, 18) ppb, and after two years 14 (9, 22) versus 10 (7, 17) ppb, all p < 0.001. All subjects were further divided into two FENO groups: <20 ppb (72%) and >= 20 ppb (28%). After one year, 81% of the participants remained in the low group and 65% in the high FENO group. After two years, 71% remained in the low group and 52% in the high FENO group. The persistent low FENO group had statistically significantly lower FEV1%pred and FVC%pred compared to the high FENO group for all three visits. Among the ex-smokers, the proportion of subjects reporting dyspnoea (mMRC >= 2) was higher in the persistent low FENO group than in the persistent high FENO group at all three visits.

In conclusion, good consistency in FENO over two years is promising for monitoring FENO during stable disease. COPD subjects with persistent low FENO had poorer lung function and reported more dyspnoea than subjects with persistent high FENO.

Aim

Identifying patients at risk for acute exacerbations of COPD (AECOPDs) is crucial to improve outcomes. We aimed to evaluate the ability of three health status instruments to predict AECOPDs in subjects with and without previous AECOPDs.

Methods

A prospective cohort study of COPD patients from primary and outpatient care in three Swedish regions. AECOPDs were retrieved from medical records. The modified Medical Research Council Dyspnoea scale (mMRC), the COPD Assessment Test (CAT), and the Clinical COPD Questionnaire (CCQ) were evaluated. Thresholds for AECOPD prediction were estimated using receiver operator characteristic (ROC) curves. Predictive values were assessed using crude and multivariable Cox regression models.

Results

We included 572 patients (59% women, age 69 +/- 8 years, FEV1 57 +/- 18% of predicted) in 2014-2016. All three instruments independently predicted future AECOPDs within three years (adjusted hazard ratio [aHR] 1.5-1.8) using thresholds mMRC >= 2, CAT >= 13, and CCQ >= 1.6. Patients without prior-year AECOPDs but high scores on all instruments had a similar AECOPD risk as those with prior AECOPDs but scores below threshold (aHR 2.4-2.5). Among patients with >= 1 AECOPD the year before inclusion and at least one of the three health status instruments above threshold, the aHR for future AECOPD during the study period ranged from 4.6 to 5.7.

Conclusions

mMRC, CAT, and CCQ were independently associated with AECOPDs over the following three-year period. The health status instruments provided additional predictive value for future AECOPDS in patients both with and without previous AECOPDs.

Abbreviations

aHR: Adjusted Hazard Ratio; AECOPD: Acute Exacerbations of Chronic Obstructive Pulmonary Disease; AUC: Area Under Curve; BMI: Body Mass Index; CAT: COPD Assessment Test; CCQ: Clinical COPD Questionnaire; COPD: Chronic Obstructive Pulmonary Disease; DAG: Directed Acyclic Graphs; FEV1: Forced Expiratory Volume in 1 Second; FVC: Forced Vital Capacity; GOLD: Global Initiative for Obstructive Lung Disease; HR: Hazard Ratio; IHD: Ischaemic Heart Disease; ICS: Inhaled Corticosteroids; IQR: Interquartile Range; mMRC: Modified Medical Research Council Dyspnoea Scale; ROC: Receiver Operator Characteristic; SD: Standard Deviation; TIE: Tools for Identifying Exacerbations

Purpose: The study aims to improve the knowledge on the associations between comorbidities, symptom burden, inflammatory biomarkers and lung function deterioration in chronic obstructive pulmonary disease (COPD).

Materials and methods: Of the 572 COPD subjects initially included in the 2014-2016 Tools for Identifying Exacerbations in COPD study in Sweden, 228 had lung function data at the 7-year follow-up. Symptom burden was assessed by the modified British Medical Research Council scale of dyspnoea (mMRC), the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ). Relative lung function decline was assessed as decline in forced expiratory volume in one second (FEV1) from baseline/year.

Results: Lower baseline symptom burden (mMRC, CAT and CCQ), higher FEV1 and FEV1% predicted, higher forced vital capacity (FVC) and having atrial fibrillation were associated with larger absolute FEV1 decline. Associations were found for having atrial fibrillation at baseline and larger relative FEV1 decline (Beta = -1.60, p = 0.005). Increased symptom burden (value at follow-up minus value at baseline), assessed by mMRC, CAT and CCQ, was positively associated with both larger absolute FEV1 decline (mMRC: Beta = 6.4, p = 0.009; CAT: Beta = 1.63, p = 0.002; CCQ: Beta = 10.6, p < 0.001) and larger relative FEV1 decline (mMRC: Beta = 0.44, p = 0.003; CAT: Beta = 0.13, p < 0.002; CCQ: Beta = 0.82, p < 0.001). Moreover, an increase in C-reactive protein (CRP) levels at follow-up was related to larger, both absolute and relative, FEV1 decline (Beta = 1.14, p = 0.031 and Beta = 0.07, p = 0.019, respectively).

Conclusions: Changes in systemic inflammation and symptom burden between two visits were positively associated with a 7-year lung function decline.

PURPOSE: Asthma control is reported to be low, often based on cross-sectional studies. There have been only a few longitudinal studies following asthma patients. We have assessed asthma control and asthma treatment over 17 years in a cohort of asthma patients.

METHODS: Patients, 18-75 years, with doctor-diagnosed asthma were randomly selected from healthcare units in Sweden. They answered questionnaires about symptoms and pharmacological treatment in 2005, 2012, and 2022. This study includes participants completing the last follow-up (n=437). Optimal asthma control was defined as no nocturnal asthma symptoms, use of short-acting β2-agonist twice or less in the past week, and no exacerbations in the last six months.

RESULTS: There was no difference in frequency of optimal asthma control (41.8% vs 40.5%, p=0.68). Inhaled corticosteroids (ICS) in combination with long-acting β2-agonists increased from 2005 to 2022 as regular maintenance treatment (40.3% vs 46.7%, p=0.009) and as reliever medicine (11.6% vs 18.9%, p<0.001). The overall use of reliever medicine more than twice in the past week did not change (48.3% vs 51.6%, p=0.24). The overall use of ICS decreased (78.0% vs 70.4%, p<0.001), as did the occurrence of having a written action plan (21.9% vs 10.4%, p<0.001). Optimal asthma control and lack of written action plans were related to discontinuation of ICS treatment.

CONCLUSION: Non-optimal asthma control is common long after diagnosis. Discontinuation of ICS may sometimes be due to optimal asthma control and no need for treatment, but lack of written action plans increases the risk of inappropriate discontinuation.