COPD profiles and treatable traits using minimal resources: identification, decision tree and stability over time.

BACKGROUND AND OBJECTIVE: Profiles of people with chronic obstructive pulmonary disease (COPD) often do not describe treatable traits, lack validation and/or their stability over time is unknown. We aimed to identify COPD profiles and their treatable traits based on simple and meaningful measures; to develop and validate a decision tree and to explore profile stability over time. METHODS: An observational, prospective study was conducted. Clinical characteristics, lung function, symptoms, impact of the disease (COPD Assessment Test-CAT), health-related quality of life, physical activity, lower-limb muscle strength and functional status were collected cross-sectionally and a subsample was followed-up monthly over six months. A principal component analysis and a clustering procedure with k-medoids were applied to identify profiles. A decision tree was developed and validated cross-sectionally. Stability was explored over time with the ratio between the number of timepoints that a participant was classified in the same profile and the total number of timepoints (i.e., 6). RESULTS: 352 people with COPD (67.4 ± 9.9 years; 78.1% male; FEV1 = 56.2 ± 20.6% predicted) participated and 90 (67.6 ± 8.9 years; 85.6% male; FEV1 = 52.1 ± 19.9% predicted) were followed-up. Four profiles were identified with distinct treatable traits. The decision tree included CAT (< 18 or ≥ 18 points); age (< 65 or ≥ 65 years) and FEV1 (< 48 or ≥ 48% predicted) and had an agreement of 71.7% (Cohen's Kappa = 0.62, p < 0.001) with the actual profiles. 48.9% of participants remained in the same profile whilst 51.1% moved between two (47.8%) or three (3.3%) profiles over time. Overall stability was 86.8 ± 15%. CONCLUSION: Four profiles and treatable traits were identified with simple and meaningful measures possibly available in low-resource settings. A decision tree with three commonly used variables in the routine assessment of people with COPD is now available for quick allocation to the identified profiles in clinical practice. Profiles and treatable traits may change over time in people with COPD hence, regular assessments to deliver goal-targeted personalised treatments are needed.

Evaluation of the genetic risk for COVID-19 outcomes in COPD and differences among worldwide populations.

BACKGROUND: Populations seem to respond differently to the global pandemic of severe acute respiratory syndrome coronavirus 2. Recent studies show individual variability in both susceptibility and clinical response to COVID-19 infection. People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups, being already associated with a poor prognosis upon infection. This study aims contributing to unveil the underlying reasons for such prognosis in people with COPD and the variability in the response observed across worldwide populations, by looking at the genetic background as a possible answer to COVID-19 infection response heterogeneity. METHODS: SNPs already associated with susceptibility to COVID-19 infection (rs286914 and rs12329760) and severe COVID-19 with respiratory failure (rs657152 and rs11385942) were assessed and their allelic frequencies used to calculate the probability of having multiple risk alleles. This was performed on a Portuguese case-control COPD cohort, previously clinically characterized and genotyped from saliva samples, and also on worldwide populations (European, Spanish, Italian, African, American and Asian), using publicly available frequencies data. A polygenic risk analysis was also conducted on the Portuguese COPD cohort for the two mentioned phenotypes, and also for hospitalization and survival to COVID-19 infection. FINDINGS: No differences in genetic risk for COVID-19 susceptibility, hospitalization, severity or survival were found between people with COPD and the control group (all p-values > 0.01), either considering risk alleles individually, allelic combinations or polygenic risk scores. All populations, even those with European ancestry (Portuguese, Spanish and Italian), showed significant differences from the European population in genetic risk for both COVID-19 susceptibility and severity (all p-values < 0.0001). CONCLUSION: Our results indicate a low genetic contribution for COVID-19 infection predisposition or worse outcomes observed in people with COPD. Also, our study unveiled a high genetic heterogeneity across major world populations for the same alleles, even within European sub-populations, demonstrating the need to build a higher resolution European genetic map, so that differences in the distribution of relevant alleles can be easily accessed and used to better manage diseases, ultimately, safeguarding populations with higher genetic predisposition to such diseases.

Saliva as a non-invasive specimen for COPD assessment.

BACKGROUND: People 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. METHODS: Outpatients 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. RESULTS: 128 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. CONCLUSION: Salivary 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.

Construct validity of the brief physical activity assessment tool for clinical use in COPD.

INTRODUCTION: Low physical activity (PA) levels are associated with poor health-related outcomes in Chronic Obstructive Pulmonary Disease (COPD). Thus, PA should be routinely assessed in clinical practice. OBJECTIVES: This study assessed the construct validity of the Brief Physical Activity Assessment Tool (BPAAT) for clinical use in COPD and explored differences in age, sex and COPD grades. METHODS: After linguistic adaptation of the tool to Portuguese, 110 patients (66.4 ± 9.6yrs, 72.7% male, FEV1  = 59.3 ± 25.5%predicted) completed the BPAAT and received an accelerometer. The BPAAT includes two questions assessing the weekly frequency and duration of vigorous- and moderate-intensity PA/walking, classifying individuals as insufficiently or sufficiently active. The BPAAT was correlated with accelerometry (moderate PA, MPA = 1952-5724 counts-per-min [CPM]); vigorous PA, VPA = 5725-∞CPM; moderate-to-vigorous PA, MVPA = 1952-∞CPM; daily steps), through: Spearman's correlations (ρ) for continuous data; %agreement, Kappa, sensitivity and specificity, positive and negative predictive values (PPV, NPV) for categorical data. RESULTS: The BPAAT identified 73.6% patients as "insufficiently active" and 26.4% as "sufficiently active". The BPAAT was weakly to moderately correlated with accelerometry (0.394 ≤ ρ ≤ 0.435, P < 0.05), except for VPA (P = 0.440). This was also observed in age (<65/≥65yrs), COPD grades (GOLD 1-2/3-4) and in male patients (0.363 ≤ ρ ≤ 0.518, P < 0.05 except for VPA). No significant correlations were found in female patients (P > 0.05). Agreement was fair to moderate (0.36 ≤ κ ≤ 0.43; 73.6% ≤ %agreement ≤ 74.5%; 0.50 ≤ sensitivity ≤ 0.52; 0.84 ≤ specificity ≤ 0.91, 0.55 ≤ PPV ≤ 0.79, 0.72 ≤ NPV ≤ 0.82). CONCLUSION: The BPAAT may be useful to screen patients' PA, independently of age and COPD grade, and identify male patients who are insufficiently active. Care should be taken when using this tool to assess vigorous PA or female patients.

Environmental Awareness for Patients with COPD Undergoing Pulmonary Rehabilitation: Is It of Added Value?

Chronic obstructive pulmonary disease (COPD) is impacted by exposure to environmental contaminants. Improving health literacy on this topic might help to optimize health outcomes. We aimed to design and deliver a health-education session about the impact of environmental contaminants on respiratory symptoms and explore participants' perceptions on such session. Patients with COPD were recruited from a pulmonary rehabilitation (PR) program. Two focus groups were first conducted to explore knowledge amongst the group. Then, the session was designed and delivered, and three focus groups were conducted to obtain feedback from participants. Data were analyzed thematically by two independent researchers. Thirty-one patients (71 ± 8 years old, FEV1 = 47.6 ± 16.8% predicted; 74.2% male) were included. Prior to the session, participants recognized the importance of this topic and described avoidance strategies to deal with symptom triggering due to air pollution. After the session, participants had their knowledge validated, kept some avoidance strategies, but also adapted some "unavoidable" activities of daily living. Patients with COPD value education on this topic, and PR offers a friendly environment to discuss prevention and management strategies. Contents of the session are provided to help deliver these sessions. Future studies could investigate the effectiveness of this intervention on self-management and exacerbations of COPD.

Minimal Clinically Important Differences for Patient-Reported Outcome Measures of Fatigue in Patients With COPD Following Pulmonary Rehabilitation.

BACKGROUND: Fatigue is a burdensome and prevailing symptom in patients with COPD. Pulmonary rehabilitation (PR) improves fatigue; however, interpreting when such improvement is clinically relevant is challenging. Minimal clinically important differences (MCIDs) for instruments assessing fatigue are warranted to better tailor PR and guide clinical decisions. RESEARCH QUESTION: This study estimated MCIDs for the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-FS), the modified FACIT-FS, and the Checklist Individual Strength-Fatigue Subscale in patients with COPD following PR. STUDY DESIGN AND METHODS: Data from patients with COPD who completed a 12-week community-based PR program were used to compute the MCIDs. The pooled MCID was estimated by calculating the arithmetic weighted mean, resulting from the combination of anchor-based (weight, two-thirds) and distribution-based (weight, one-third) methods. Anchors were patients' and physiotherapists' Global Rating of Change Scale, COPD Assessment Test, St. George's Respiratory Questionnaire (SGRQ), and exacerbations. To estimate MCIDs, we used mean change, receiver-operating characteristic curves, and linear regression analysis for anchor-based approaches, and 0.5 × SD, SE of measurement, 1.96 × SE of measurement, and minimal detectable change for distribution-based approaches. RESULTS: Fifty-three patients with COPD (79% male, 68.4 ± 7.6 years of age, and FEV1 48.7 ± 17.4% predicted) were included in the analysis. Exacerbations and the SGRQ-impact and the SGRQ-total scores fulfilled the requirements to be used as anchors. Pooled MCIDs were 4.7 for FACIT-FS, 3.8 for the modified FACIT-FS, and 9.3 for the Checklist Individual Strength-Fatigue Subscale. INTRPRETATION: The MCIDs proposed in this study can be used by different stakeholders to interpret PR effectiveness. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03799666; URL: www.clinicaltrials.gov.